This presentation provides information about the regulatory system for pharmaceutical manufacturers and GMP inspections in the European Union. It is compiled by Drug Regulations, a nonprofit organization that provides online resources for pharmaceutical professionals. The presentation explains that the EU has a harmonized system where the same rules and procedures apply in all 28 member states, which is overseen by the European Medicines Agency and national competent authorities. Manufacturers supplying products to the EU must comply with Good Manufacturing Practice standards and are subject to regular inspections.
Regulatory requirnment and approval procedure of drugs in japan pptsandeep bansal
this ppt is about all the rules and regulations of drugs in Japan.this ppt contains the PMDA structure, DMF data, IND and NDA procedure, cosmetic regulations, post marketing survelliance etc.
Regulatory requirnment and approval procedure of drugs in japan pptsandeep bansal
this ppt is about all the rules and regulations of drugs in Japan.this ppt contains the PMDA structure, DMF data, IND and NDA procedure, cosmetic regulations, post marketing survelliance etc.
plasma master file is a EU requirement for the apploval of the biologics or the biosimilars to the EU in a eCTD format or Nees as per the requirement type and should contain the above given details
Herbal medicines are popular because of experience and the abundant
availability of plants in India due to its varied climatic zones. India has
around 45,000 species of plants, out of which 15,000–20,000 plants have
proven medicinal value.
Georgina Gal, Regulatory Affairs Manager, AbbVie, Hungary
Presentation at EIPG – BIPA Symposium “Clinical Trials Research” at the Faculty of Pharmacy, Medical University of Sofia, Sofia 2014.
Understanding FDA Requirements Medical Devicesmarchell
The medical device market is experiencing explosive growth. Currently valued at $90 billion, market growth will continue to accelerate as demographics and market drivers increase their pressure for new and innovative product offerings.
Moreover, a substantial investment of time and resources is required to properly evaluate a new product idea and estimate its potential for success. So when a company executive declines a seemingly good product idea, what is probably being declined is the expense of properly evaluating the idea, and after having paid these expenses, the prospect of embarking on an expensive commercialization effort that has a 90 percent chance of failing.
plasma master file is a EU requirement for the apploval of the biologics or the biosimilars to the EU in a eCTD format or Nees as per the requirement type and should contain the above given details
Herbal medicines are popular because of experience and the abundant
availability of plants in India due to its varied climatic zones. India has
around 45,000 species of plants, out of which 15,000–20,000 plants have
proven medicinal value.
Georgina Gal, Regulatory Affairs Manager, AbbVie, Hungary
Presentation at EIPG – BIPA Symposium “Clinical Trials Research” at the Faculty of Pharmacy, Medical University of Sofia, Sofia 2014.
Understanding FDA Requirements Medical Devicesmarchell
The medical device market is experiencing explosive growth. Currently valued at $90 billion, market growth will continue to accelerate as demographics and market drivers increase their pressure for new and innovative product offerings.
Moreover, a substantial investment of time and resources is required to properly evaluate a new product idea and estimate its potential for success. So when a company executive declines a seemingly good product idea, what is probably being declined is the expense of properly evaluating the idea, and after having paid these expenses, the prospect of embarking on an expensive commercialization effort that has a 90 percent chance of failing.
TGA presentation: AusMedtech, 24 May 2017 TGA Australia
This presentation outlines reforms to the device regulatory system following the Expert Panel Review of Medicines and Medical Devices Regulation, reforms to the in vitro diagnostic devices (IVD) regulatory framework, reforms to the European and IVD system and the TGA's new Clinical Evidence Guidelines.
Regulatory Approval Process for Medical Devices in EU - Presentation by Aksha...Akshay Anand
A presentation on Regulatory Approval Process for Medical Devices in European Union that explains in brief about the various aspects including the EU Medical Device Directives, Classifications, CE Certification, Medical Device Registration & Timelines. This was presented as a part of curriculum by Akshay Anand in JSS College of Pharmacy, Mysuru during January 2015
Regulations for drug approval in USA, E.U & India
Pharmaceutical industry is the most regulated of all the industries. Regulations are put in order to develop the most efficient and safe pharmaceutical products. It takes more than 8 to 15 years to develop a new drug product & costs more than $ 800 million.
It a detailed description of European Union and Medicines and Healthcare Products Regulatory agency with documentation process of filing MAA application.
Medicinal products are highly regulated in the European Union (EU) and are subject to a separate, complicated system of approvals that governs how, when, where, and in what form such products will be allowed to be sold within the borders of the EU.
Pharmaceutical regulatory systems in the EU comprise a decentralized body called the European Medicines Agency (EMA), Heads of Medicines Agencies (HMA), National Competent Authorities (NCAs) and European Directorate for the Quality of Medicines (EDQM). and collection of rules and regulations governing medicinal products in the EU is Eudralex.
The European Medicines Evaluation Agency (EMEA) was established in London, in the year 1995, to coordinate the European Union (EU) member states for evaluating and controlling the medicinal products for both human and veterinary use
The European medicines regulatory system is based on a network of around 50 regulatory authorities from the 31 EEA countries (28 EU Member States plus Iceland, Liechtenstein and Norway)
EMA is responsible for the scientific evaluation, essentially of innovative and high-technology medicines developed by pharmaceutical companies for use in the EU.
EMA has various committees for various categories of medicinal products
Committee for Medicinal Products for Human Use (CHMP)
Pharmacovigilance Risk Assessment Committee (PRAC)
Committee for Medicinal Products for Veterinary Use (CMVP)
Committee for Orphan Medicinal Products (COMP)
Committee on Herbal Medicinal Products (HMPC)
Committee for Advanced Therapies (CAT)
Paediatric Committee (PDCO)
For a medicinal product to seek market authorization in Europe, the manufacturer or sponsor shall choose a pathway from four different pathways based upon the type of medicinal substance, and requirements such as a number of countries chosen for marketing, timeline, etc.
EMA Guidelines for Clinical Trial Management - Pepgra HealthcarePEPGRA Healthcare
The European Medicines Agency (EMA) relies on the results of clinical trials carried out by pharmaceutical companies to reach its opinions on the authorisation of medicines. EMA guidelines for clinical trial regulations adopted in 2014 aim to make it easier for the clinical trials companies while empowering participants through transparency.
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Website : https://bit.ly/33Fwsye
Email us: sales.cro@pepgra.com
Whatsapp: +91 9884350006
Medicines Verification Systems in Europe – a perspective from wholesale distr...László Árvai
The Falsified Medicines Directive and its Delegated Regulation on Safety Features
European Medicines Verification Organisation (EMVO) and the roll-out of National Medicines Verification Systems
GIRP and wholesale distributors perspectives on medicines verification systems
Impact on the actors in the supply chain
Annual report 2015 - European Directorate for the Quality of Medicines & Heal...Council of Europe (CoE)
This publication presents the work carried out in 2015 by the European Directorate for the Quality of Medicines & HealthCare, Council of Europe, highlighting its particular achievements.
This presentation highlights the reasons which lead to the withdrawal of the 2002 Guidance of the FDA and the current issue with Blend Uniformity and Content Uniformity Determinations.
WHO has recently issued draft document titled "Guidelines on Validation". These guidelines (i.e., the main text included in this working document) cover the general principles of validation and qualification.
These guidelines focus mainly on the overall concept of validation and are not intended to be prescriptive in specific validation requirements. This document serves as general guidance only and the principles may be considered useful in its application in the manufacture and control of starting materials and finished pharmaceutical products (FPPs), as well as other areas. Validation of specific processes and systems, for example, in sterile product manufacture, requires much more consideration and a detailed approach that is beyond the scope of this document. The general text in this document may be applicable to validation and qualification of premises, equipment, utilities, systems, processes, and procedures.
The draft on the specific topics, the appendices to this main text, will follow. The following is an overview on the appendices that are intended to complement the text of this working document:
Appendix 1: Validation of heating, ventilation and air-conditioning systems - will be replaced by cross reference to WHO Guidelines on GMP for HVAC systems for considerations in qualification of HVAC systems (update - working document QAS/15.639/Rev. 1)
Appendix 2: Validation of water systems for pharmaceutical use - will be replaced by cross-reference to WHO Guidelines on water for pharmaceutical use for consideration in qualification of water purification systems
Appendix 3: Cleaning validation - consensus to retain
Appendix 4: Analytical method validation - update in process
Appendix 5: Validation of computerized systems - update in process
Appendix 6: Qualification of systems and equipment - update in process
Appendix 7: Non-sterile process validation - update already published as Annex 3, WHO Technical Report Series, No. 992, 2015
Comments on this draft document are due by July 12, 2016.
A presentation on this guidance is given below:
Presentation on New WHO Guidance on Validations
Environmental Monitoring describes the microbiological testing under- taken in order to detect changing trends of microbial counts and micro- flora growth within cleanroom or controlled environments. The results obtained provide information about the physical construction of the room, the performance of the Heating, Ventilation, and Air-Conditioning (HVAC) system, personnel cleanliness, gowning practices, the equipment, and cleaning operations.
Over the past decade, environmental monitoring has become more sophisticated in moving from random sampling, using an imaginary grid over the room and testing in each grid, to the current focus on risk assessment and the use of risk assessment tools to determine the most appropriate methods for environmental monitoring.
This presentation gives current trends in the application of risk assessment to the practice of environmental monitoring.
This presentation is compiled from freely available resources like the websites of FDA, EMA ,WHO and research papers published by experts in this field like Sandle, T Reinmüller, B , Hyde, W,, Costello, E.K., Lauber, C. L., Hamady, M., Fierer, N., Gordon, J.I., Knight, R.
Paper published by T. Sandle on clean room contamination was referred extensively for this presentation. “Drug Regulations” is a non profit organization which provides free online resource to the Pharmaceutical Professional.
Visit http://www.drugregulations.org for latest information from the world of Pharmaceuticals.
This presentation gives an overview of : Validation of microbiological methods , Considering some of the limitations and
Key criteria that may be applicable for assessment.
More from GMP EDUCATION : Not for Profit Organization (20)
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Pharynx and Clinical Correlations BY Dr.Rabia Inam Gandapore.pptx
Presentation on EU Regulatory & Quality System.
1. This presentation is compiled by “ Drug Regulations”
a non profit organization which provides free online
resource to the Pharmaceutical Professional.
Visit http://www.drugregulations.org for latest
information from the world of Pharmaceuticals.
10/17/2015 1
2. This presentation is compiled from freely available
resource like the website of EMA & EU.
“Drug Regulations” is a non profit organization
which provides free online resource to the
Pharmaceutical Professional.
Visit http://www.drugregulations.org for latest
information from the world of Pharmaceuticals.
10/17/2015 2
Drug Regulations : Online Resource for Latest Information
3. The regulatory system for supervision of
pharmaceutical manufacturers and GMP
inspection in the European Union is one of the
most advanced in the world.
This system is often poorly understood outside
the EU nations
This presentation gives an explanation of the
EU system.
10/17/2015 3Drug Regulations : Online Resource for Latest Information
4. The European Union includes 28 Member States
located in Europe, which are:
◦ Austria, Belgium, Bulgaria, Croatia, Cyprus, Czech Republic,
Denmark, Estonia, Finland, France, Germany, Greece,
Hungary, Ireland, Italy, Latvia, Lithuania, Luxemburg, Malta,
Netherlands, Poland, Portugal, Romania, Slovakia, Slovenia,
Spain, Sweden, and United Kingdom.
The EU total population is about 500 million
people.
10/17/2015 4Drug Regulations : Online Resource for Latest Information
5. The European Union operates through a system of
◦ Supranational independent institutions and
◦ Intergovernmental negotiated decisions by its Member
States.
It is a legal entity and can negotiate international
agreements on behalf of its Member States.
10/17/2015 5Drug Regulations : Online Resource for Latest Information
6. Three main EU institutions.
◦ The European Parliament,
◦ The Council of the European Union and
◦ The European Commission
Ordinary Legislative Procedure
◦ Produces Policies and laws that apply throughout the
European Union are formulated by this process.
(formerly "co-decision")
10/17/2015 6Drug Regulations : Online Resource for Latest Information
7. The European Union has developed a single market
◦ Standardized system of laws that apply in all its Member
States.
Authorization of medicines and the supervision of
safety of medicines.
◦ Same rules and harmonized procedures apply to all the 28
Member States
10/17/2015 7Drug Regulations : Online Resource for Latest Information
8. Regulatory system based on a network of
decentralized National Competent Authorities
(NCAs) in the Member States,
Supported and coordinated by a centralized
agency, the European Medicines Agency. (EMA).
◦ Link to EMA website
10/17/2015 8Drug Regulations : Online Resource for Latest Information
9. The EMA was created in 1995 to coordinate the existing
scientific resources in the EU Member States
EMA: an interface for cooperation and coordination of
Member States’ activities with respect to medicinal products.
EMA scientific decisions are made through its scientific
committees.
◦ Members are chosen on the bases of their scientific expertise and are
appointed by the Member States.
One of the main roles of EMA is to mobilize scientific
resources in the Member States.
◦ Many of its scientific activities are carried out through a large network of
scientific experts made available by the Member States.
10/17/2015 9Drug Regulations : Online Resource for Latest Information
10. The European Commission’s role is multifaceted and focuses on the
following:
◦ Right of initiative: To propose new or amending legislation for the pharmaceutical
sector
◦ Implementation: To adopt implementing measures as well as to ensure and monitor
the correct application of EU law
◦ Risk management: To grant EU-wide marketing authorizations for centralized
products or maximum residue limits on the basis of a scientific opinion of the EMA
Supervisory authority:
◦ To oversee the activities of the EMA in compliance with the mandate of the EMA, EU
law and the EU policy objectives Global outreach:
◦ To ensure appropriate collaboration with relevant international partners and to
promote the EU system globally
10/17/2015 10Drug Regulations : Online Resource for Latest Information
11. System for Marketing Authorization (MA) of medicines & the
referral procedure,
European Commission, the EMA and the Member States
cooperate to a great extent in its implementation
The EU national, decentralized and mutual recognition MA
procedures coexist with the centralized procedure
◦ Marketing Authorization Procedure
◦ See table in next slide.
10/17/2015 11Drug Regulations : Online Resource for Latest Information
13. An EU binding mechanism
◦ Ensures that the same measures are applied to products subject to
national, decentralized and mutual recognition MA procedures.
This procedure may be notably invoked when
◦ The conditions of authorizations need to be reviewed in the light of
quality, safety and efficacy data (Union Interest Referral),
◦ Member States have adopted different decisions regarding products that
are authorized in at least two Member States (Divergent Decision Referral).
◦ In the absence of agreement among Member States in the course of the
mutual recognition or decentralized authorization procedures
(Mutual Recognition and Decentralised Referral).
10/17/2015 13Drug Regulations : Online Resource for Latest Information
14. This mechanism involves an opinion from the appropriate
EMA committee.
Results in a decision of the European Commission that is
binding for all Member States
See link for details
10/17/2015 14Drug Regulations : Online Resource for Latest Information
15. Fundamental aspect
Legislation applicable to pharmaceuticals in the European
Union is the same irrespective of the Member State or
authorization route of the product, as it is developed at Union
level.
See the link
10/17/2015 15Drug Regulations : Online Resource for Latest Information
16. Clinical trials of Investigational Medicinal Products (IMPs)
require
◦ Authorization by each NCA and
◦ A favorable opinion by an ethics committee in which the clinical trial takes
place and is granted in the form of a Clinical Trial Authorization (CTA)
◦ (http://ec.europa.eu/health/human-use/clinical- trials/index_en.htm).
The assessment for a CTA takes into account the holding of
an appropriate authorization for each EU site of manufacture
or importation.
10/17/2015 16Drug Regulations : Online Resource for Latest Information
17. Any manufacturer, no matter where it is located, must comply
with GMP if they are to supply products to the EU.
There is a single system for GMP supervision of
manufacturers which is valid throughout all the EU Member
States;
This applies to
◦ Authorized medicinal products for human or veterinary use placed on the
market and
◦ IMPs used in clinical trials.
10/17/2015 17Drug Regulations : Online Resource for Latest Information
18. The system is based on two main pillars,
◦ The authorization/registration of operators in the supply
chain and
◦ Inspection of those operators
To ensure compliance with
legal requirements,
GMP
Requirements in the MA or CTA.
10/17/2015 18Drug Regulations : Online Resource for Latest Information
19. Manufacturers and importers of medicinal products located in
the EU need to be authorized to carry out their activities.
This obligation also applies to manufacturers and importers of
products only intended for export and IMPs.
The C A of each Member State are responsible for granting the
authorizations
A condition for grant of a manufacturing or import authorization
is that the manufacturers must comply with EU GMP.
10/17/2015 19
Drug Regulations : Online Resource for Latest Information
20. GMP principles and guidelines are set out in two
Directives
◦ One for medicines for human use and
◦ The other for medicines for veterinary use.
More detailed guidelines have been developed
through the work of the GMP and GDP Inspectors
Working Group
see Link
10/17/2015 20
Drug Regulations : Online Resource for Latest Information
21. Manufacturers and importers of medicinal products located in the European
Union or manufacturers located in a third country are regularly inspected by
an EU competent authority for compliance with EU GMP.
The outcome of these inspections must be accepted by all other EU
authorities.
After every inspection a GMP certificate (positive outcome) or noncompliance
report (negative outcome) must be issued by the inspecting authority
This is entered in the Eudra GMDP database, which is accessible by
regulators in other countries.
Most of this information is also available to the general public.
See Link
10/17/2015 21Drug Regulations : Online Resource for Latest Information
22. Inspections of manufacturers are typically requested in order to
Grant or maintain a manufacturing or import authorization (EU sites)
or
Assessment, approval and maintenance of an MA (typically sites
outside the EU) or CTA.
◦ For example, EMA may request that an EU competent authority undertake a
preapproval GMP inspection of a site included in a MA application through the
Centralized procedure or
◦ That an EU competent authority undertake periodic repeated post authorization
surveillance inspections of sites named in centralized MAs,
◦ In order to verify ongoing compliance with GMP and that the requirements of the MA
are being met.
10/17/2015 22
Drug Regulations : Online Resource for Latest Information
23. According to EU legislation, the interval for
repeated GMP inspection should be based on risk.
As a result, a procedure outlining a risk-based
model to frequency of inspections is included in
the Compilation of European Union Procedures on
Inspections and Exchange of Information
See Link
10/17/2015 23
Drug Regulations : Online Resource for Latest Information
24. Manufacturers, importers and distributors of active
substance located in the European Union are
required to comply with GMP
Must be registered to the National Competent
Authority of the Member State where they are
located.
10/17/2015 24
Drug Regulations : Online Resource for Latest Information
25. For active substances manufactured outside the EU and
imported:
◦ Each batch needs to be accompanied by a written confirmation
◦ This should be issued by the competent authority of the country
where it is produced
◦ W C should Confirm among other things, that GMP at least
equivalent to that in place in the European Union has been applied
to its manufacture.
◦ The C Aof the exporting country also needs to confirm that any GMP
noncompliance arising at the manufacturing site would be
communicated to the European Union.
The receipt of this noncompliance information is via the EMA.
10/17/2015 25Drug Regulations : Online Resource for Latest Information
26. The requirement for the written
confirmation can only be waived
◦ If the third country is included by the European
Commission, after assessment, in a list of countries with an
equivalent system of supervision and inspection or,
◦ Exceptionally, in order to ensure availability of medicines in
the EU market, if a GMP certificate for the site has been
issued by an EU competent authority after inspection.
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27. The requirement for written confirmation, introduced from July 2013
by Directive 2011/62/EU requires that authorities outside of the EU
take responsibility for active substances manufactured in their
territory, if exported to the EU.
◦ See Link
This requirement caused some debate before its implementation
There were concerns on its potential to cause shortages in the EU, if
the exporting authorities were not willing or able to provide the
written confirmations,
However this was not the case and countries gave a written
confirmation.
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28. The EU legislation places the responsibility for using active
substances manufactured in compliance with GMP on
◦ The medicinal product manufacturer or
◦ The importer (in case the medicinal product is manufactured outside the European
Union).
The holder of the MA or EU importer must
◦ Verify the registration status of the manufacturer of the active substance and
◦ verify compliance by the manufacturer of active substance with GMP,
This should be done by conducting audits at the manufacturing site.
This compliance can be implemented directly or with use a third
party acting under a contract.
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29. Inspections of active substance manufacturers are carried out by EU
competent authorities following a risk-based approach, or if there is
suspicion of noncompliance.
See Link
Furthermore, every application for an MA must include a confirmation
that the holder of the MA has verified compliance of the manufacturer of
the active substance with principles and guidelines of GMP.
The confirmation shall contain a reference to the date of the audit
A declaration by the Qualified Person that the outcome of the audit
confirms that the manufacturing complies with GMP principles and
guidelines.
See Link
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30. Inspections of active substance manufacturers may also be
organized by the European Directorate for the Quality of Medicines &
Healthcare (EDQM) of the Council of Europe, on behalf of the EU.
See Link
The Council of Europe has 47 members including all EU Member
States and it has close cooperation with the EU.
EDQM is responsible for developing and maintaining the European
Pharmacopoeia.
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31. EDQM issues Certificates of Suitability with the monographs of the
European Pharmacopoeia (CEP) that can replace most of the data
normally expected in EU MA dossiers for the active substance.
See Link
In order to issue and maintain these certificates, EDQM runs its own
inspection program of active substance manufacturers.
Most of the inspections organized by the EDQM are carried out by
inspectors from EU inspectorates.
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32. Inspections are carried out by inspectorates of Member States.
In order to avoid duplication it is necessary to identify the Member
State responsible for supervision and inspection of any
manufacturing sites for the EU market.
This is achieved through the identification of one or more
Supervisory Authority (SA);
The SA is the NCA in the EU responsible for the GMP supervision of
the site, including granting the manufacturing or import
authorization and GMP inspection.
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33. If the manufacturing site is in the EU, the SA is the NCA of the
Member State where the site is located.
In cases where the manufacturing site is outside the EU, the SA is
the NCA of the Member State in which the importer of the product(s)
is located.
Where products from a manufacturing site located in a country
outside the EU are imported in more than one Member State, there
may be more than one SA, which cooperate in the supervision of the
manufacturing site.
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34. An important feature of the supervision system in place in Europe is
the role of Qualified Person (QP).
In order to obtain an authorization, EU manufacturers and importers
must have at their disposal the services of at least one Qualified
Person
The Qualified Person must
◦ Take responsibility for securing that each batch of medicinal product, manufactured
or imported, has been manufactured in accordance with EU GMP, and
◦ Must certify compliance with GMP and with the relevant MA(s).
◦ See Link
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35. A batch may only be released by a manufacturer or importer for
distribution in the EU after certification by the QP.
Member States are empowered to take administrative and
disciplinary measures against QPs if they have failed to fulfil their
obligations.
Furthermore, imported batches need to undergo a full retest in the
EU to ensure the quality of the product in accordance with the MA
specification.
There-testing requirement is waived if there is an operational
Mutual Recognition Agreement in place between the EU and the
exporting country.
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36. The discovery of serious GMP noncompliance may have implications
for the Member State, which carries out the inspection, and all
Member States.
International authorities would also be involved if the active
substance or product be supplied to them.
A mechanism that ensures a coordinated approach for protection of
public and/or animal health is taken throughout the European Union
.
See Link
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37. Objective of this Procedure:
◦ Achieve a coordinated and harmonized assessment
◦ Proportionate supervisory actions
◦ Balance the protection of patients and minimize supply
disruptions
◦ Ensure maximum efficiency
◦ Avoid full parallel reviews on a national level across the
European Union.
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38. European legislation provides that manufacturer
and import authorizations may be suspended or
not granted as a result of noncompliance with GMP.
Also, existing MAs for the products affected can be
varied, not granted or revoked.
Urgent measures include
◦ Prohibition of manufacture, importation or supply, and/or
◦ Withdrawal of all, or of specific batches from the market.
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39. EUDRA GMDP is a publicly accessible Union database
◦ See Link
A repository of
◦ Manufacturing and import authorizations,
◦ GMP certificates and
◦ Non-compliance reports.
After every GMP inspection carried out by an EU competent
authority following information is entered in the database.
◦ A GMP certificate (positive outcome) or
◦ A noncompliance report (negative outcome)
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40. The database includes a planning module (only accessible to the relevant
regulators) for coordination of inspections planned by EU authorities in countries
outside the European Union.
Data are entered into the planning module in order to facilitate exchange of
information between competent authorities and reduce duplication and ensure the
best use of inspectional resources.
EMA and EU authorities recognize the global nature of modern pharmaceutical
supply chains
They also recognize the need for close collaboration and cooperation with
regulatory authorities outside the European Union
Therefore work is ongoing to extend the use of the EudraGMDP database planning
module to include exchange of information on inspections planned by authorities
outside the European Union.
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41. All the National inspectorates in the Member States should be
equivalent as regards the level of supervision they are able to
provide.
A number of measures are put in place to ensure that this is
the case, summarized in subsequent slides
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42. Legislation
◦ The pharmaceutical legislation is developed at EU level.
◦ This is mainly in the form of Regulations and Directives.
◦ Both are applicable to all the Member States.
◦ Regulations are directly applicable to the entire EU territory.
◦ Directives have to be transposed into national legislation, in
a timeframe established in the Directive itself, usually 18
months.
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43. Legislation
The EU legal framework for medicinal products is intended to ensure
a high level of public health protection and to promote the
functioning of the EU internal market.
The system is also designed to encourage innovation.
It is a large body of legislation that ensures extensive harmonization
within the European Union, including GMP and inspections.
The pharmaceutical legislation is published in the Official Journal of
the European Union.
◦ http://eur- lex.europa.eu/oj/direct-access.html
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44. The EU GMP guide
A single GMP guide is in use in the European Union.
See Link
The guide is referenced in the EU legislation
◦ Directives 2001/83/EC for human products,
◦ 2001/82/EC for veterinary products and in clinical trial legislation
◦ See Link
This has long since replaced any previously existing national
GMP guide.
The EU GMP guide provides the standards and requirements used
by EU inspectors for any GMP inspections
◦ Both in or outside of the European Union.
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45. The EU GMP guide
The guide is subdivided into tree parts and 19 annexes dealing
with specific types of manufacture.
Part 1 is the GMP for finished products
Part 2 GMP for active substances
Part 3 includes GMP-related documents
The EU GMP guide is harmonized with the PIC/S GMP guidelines
on an ongoing basis.
EU GMP Part 2 reflects the EU’s agreement to the ICH Q7
guidelines and forms the basis of the detailed guidelines.
The Compilation of European Union Procedures on Inspections
and Exchange of Information
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46. The Compilation of European Union Procedures on Inspections and
Exchange of Information
The Compilation of European Union Procedures on Inspections and
Exchange of Information (CoUPs) is a collection of procedures for
GMP and Good Distribution Practice (GDP).
◦ See Link
This is applicable to all the inspectorates in the European Union.
It provides a tool to facilitate cooperation between EU Member States
and a means to achieve harmonization.
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47. The Compilation of European Union Procedures on
Inspections and Exchange of Information
The CoUP covers,
◦ The basis for national procedures that form part of the
national inspectorates’ quality systems,
◦ How quality defects and noncompliance are handled and
◦ How GMP and GDP inspections are carried out and
reported.
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48. The Compilation of European Union Procedures on Inspections and Exchange of
Information
The contents of the CoUP are constantly updated, developed and agreed,
This is coordinated by EMA, by representatives of the Inspectorates of each Member
State, including those supervising the manufacture and import of veterinary medicinal
products only.
Once agreed, they are adopted by the European Commission and then published on its
behalf by the EMA.
Common Union formats for manufacturing and import authorizations, GMP certificates
and for statements of non-compliance with GMP have been agreed and published in the
compilation
EU competent authorities have implemented them in order to enhance communication,
collaboration and co- operation between authorities.
This common format enables Member States to enter manufacturing, importing and
distribution authorizations in the Union database, EudraGMDP
See Link
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49. The GMP/GDP Inspectors Working Group
The GMP/GDP Inspectors Working Group (GMDP IWG) is a group of
senior inspectors appointed by all the EEA competent authorities.
◦ SEE LINK
They meet at EMA premises four times a year
It is chaired by EMA
A European Commission representative attends the meetings,
Also observers from the European EDQM accession countries
(countries which have applied to be part of the EU but have not
joined yet) and MRA partners attend the meeting.
Representatives from other international authorities can be invited
on a case-by-case basis
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50. The GMP/GDP Inspections Working Group
The group is a forum for harmonization and discussion of common
issues which are taken by the inspectors back to their NCA for
implementation.
Any new or amended text of the EU GMP guide is developed by this
group, with the European Commission responsible for the final
adoption.
The GMDP IWG also maintains the CoUP and oversees, on behalf of
the Heads of Medicines Agencies (HMAs) the Joint Audit Programme.
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51. Training
The GMDP IWG organises training for EEA inspectors and inspectors
from accession countries, aimed at raising the technical capability of
the inspectors,
This ensures common understanding of issues related to GMP and
harmonization.
In addition, EMA has signed a partnership agreement with PIC/S on
cooperation on training for GMP inspectors, which recognizes the
role that PIC/S plays in this area and avoids duplication of effort.
See Link
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52. Ensuring Equivalence before Joining the EU
Becoming a member of the European Union is a complex procedure
There are strict conditions for EU membership to ensure that new
members are admitted only when they are fully able to take on the
obligations of membership,
This includes compliance with all the EU’s standards and rules.
For the purpose of accession negotiations, these are divided into 35
different policy fields (chapters). Link
For acceding to the EU, a candidate country must implement the EU rules
and regulations in all areas.
The length of the membership negotiations can vary and depends on the
time needed to complete the necessary reforms and the alignment with
EU law.
The candidates are supported financially, administratively and
technically during this pre-accession period.
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53. Ensuring Equivalence before Joining the EU
In order to ensure that new Member States joining the European
Union have reached the same level as the other members before the
date of accession, a number of measures are put in place. These
include:
◦ The European Commission checks compliance with the EU legislation (including
pharmaceutical legislation)
◦ Through the TAIEX program (Link) financed by the European Commission, technical
support may be provided
◦ Accession countries are invited as observers to EU meetings (including the GMDP IWG)
◦ Specific training on EU procedures is organized
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54. Auditing is an important part of the measures put in place in order to
oversee the equivalence of Member States.
There are a number of contexts in which Member States NCAs and/or
inspectorates can be audited.
The Joint Audit Program (JAP) of the EU NCAs’ GMP inspectorates is an
internal audit program under the Heads of Medicines Agencies (HMA)
◦ Link
This is run on behalf of HMA by the GMDP IWG.
JAP aims at achieving and maintaining equivalence between Member
States’ national inspectorates responsible for GMP.
It was established in October 2000 and is an important part of the
quality system adopted by all GMP inspectorates in the EU.
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55. JAP auditors are senior GMP inspectors, further qualified for auditing
inspectorates through specific training.
A list of qualified JAP auditors is maintained by the Compliance Group,
which is a subgroup of the GMDP IWG.
Link
JAP auditors also provide technical advice and support to accession
countries before they become EU Member States.
EU inspectorates are audited through the JAP onsite, at intervals
established through a risk-based approach (typically every five to six
years).
Mutual Recognition Agreement and other international partners are
invited on a case-by-case basis to join JAP audits of EU Member States
inspectorates as observers.
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56. Audits are also organized in the framework of the Pharmaceutical
Inspection Convention and Pharmaceutical Inspection Co-operation
Scheme ,jointly referred to as PIC/S and Mutual Recognition
Agreement (MRA
See Link
Since most of the EU authorities and all MRA partners are member of
PIC/S, synergies between the various audit schemes are used in
order to avoid duplication.
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57. The Benchmarking of European Medicines Agencies
See Link
(BEMA) is an internal EU program managed by the Heads of Medicines
Agencies,
This is based on assessment of the systems and processes in individual
agencies against a set of indicators in four main areas:
◦ Management systems
◦ Assessment of marketing authorization applications
◦ Pharmacovigilance (drug safety) activities
◦ Inspection services
The assessment identifies strengths and best practices in agencies and
any opportunity for improvement.
The program has concluded its third cycle in 2015.
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58. The European Union and its Member States are involved in several
bilateral and multilateral cooperation activities with international
partners in the GMP area.
The main advantage is that international cooperation allows, by
relying on information received from trusted international
authorities, to reallocate foreign inspections towards areas more at
risk.
It thus optimizes available inspection resources.
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59. PIC/S
Pharmaceutical Inspection Convention and Pharmaceutical Inspection
Co-operation Scheme
Jointly referred to as PIC/S
http://www.picscheme.org/pics.php
Aims at harmonizing inspection procedures worldwide
Develops common standards in the field of GMP
Provides training opportunities to inspectors.
Facilitates cooperation and networking between competent authorities,
regional and international organizations.
Most EU Member States are members of PIC/S while EMA is participating
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60. Mutual Recognition Agreements ( MRA’s)
Link
Official agreements on the mutual recognition of assessment of
conformity of regulated products, which are negotiated and signed at EU
level.
MRAs concluded by the European Union include pharmaceuticals and
cover GMP.
Consequently, inspection results carried out by MRA partners in their
territory are recognized by EU Member States and vice versa
Retesting upon importation into the European Union is not needed in the
QP batch certification process.
The MRA scope can cover both human and veterinary products, finished
products, active substances and Investigational Medicinal Products.
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61. There are differences in scope between the various MRAs.
Currently, the European Union has operational MRAs in place with Australia,
Canada, Japan, New Zealand and Switzerland.
The EU also has in place an Agreement on Conformity Assessment and
Acceptance of industrial products (ACAA), which includes GMP, with Israel.
An ACAA is a specific type of MRA;
The main practical difference is that in the ACAA case results of inspections
carried out outside the territory of the agreement partners are mutually
recognized as well, in addition to inspections carried out in the partners’
territory.
An MRA between the European Union and the United States was signed in
1999; at the time of this writing it is operational only toward rapid alerts.
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62. International Coalition of Medicines Regulatory Authorities (ICMRA).
Link
The European Commission, EMA and some EU Member States participate to the
activities of the International Coalition of Medicines Regulatory Authorities
◦ (France, Germany, Ireland, Italy, Spain and UK)
Recent initiative
Started by Heads of Medicines Agencies worldwide,
Aims at providing global strategic coordination and direction on areas that are
common to many regulatory authorities’ missions worldwide,
Builds on existing arrangements such as those of PIC/S.
The ICMRA has the objective to establish synergies and to foster global
cooperation among regulators and GMP is one of the ICMRA main areas of
interest.
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63. Other International Cooperation Activities
In addition to MRAs, the European Union is involved in several less
formalized cooperation schemes on GMP with international partners and/or
in areas not covered by an MRA
API international cooperation project
Main objectives are the sharing of information on inspection planning, policy
and inspection reports and joint inspections on manufacturers located
outside the participating countries.
It includes the following participants:
The EMA and all EU member States, the European EDQM, the U.S. FDA, the
Australian Therapeutic Goods Administration (TGA) and WHO.
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64. Several bilateral pilots and programs between EMA and FDA were also developed
during the last ten years with the view to increase collaboration on domestic and
third country GMP inspections.
This less formal form of cooperation in the last years has allowed the building of
confidence among cooperating countries and regions, mainly through joint
inspections and exchange of information
Link
It is opening new possibilities of mutual reliance on inspection results.
In this perspective, it is worth noting that the European Union has identified the
recognition of GMP inspections carried out in the European Union and the United
States and in third countries as a main objective for the pharmaceutical sector in
the context of the negotiations of the Transatlantic Trade and Investment
Partnership
Link
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65. This presentation is compiled from freely available
resource like the website of EMA & EU.
“Drug Regulations” is a non profit organization
which provides free online resource to the
Pharmaceutical Professional.
Visit http://www.drugregulations.org for latest
information from the world of Pharmaceuticals.
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