Firsthand overview of the TGA's Pharmacovigilance Inspection programme from the perspective of both the TGA and companies that have participated in the 'Pilot Inspection Programme'.
Online Clinical Trial Notification (CTN)TGA Australia
A brief overview of the clinical trials environment including the role of the Clinical Trial Jurisdictional Working Group and the Framework for Action (2) Provide an update on progress over the last year on key projects (3) Outline the importance of leadership and collaboration to maintain the momentum of improvements.
Presentation: The Australian Pharmacovigilance Inspection Program (PVIP)TGA Australia
Presentations given at the TGA information sessions cover the pharmacovigilance inspection guidelines, preparing for inspections, inspection process, and close out of inspections.
Presentation: Spotlight on prescription medicine post-market reformsTGA Australia
An overview of reform initiatives relevant to prescription medicines pharmacovigilance arising from the Review of Medicines and Medical Devices Regulation.
Presentation: Spotlight on prescription medicines reformsTGA Australia
An overview of initiatives arising from the Review of Medicines and Medical Devices Regulation relevant to prescription medicines as well as orphan drugs and developments for eCTD and the new MedSearch app.
Presentation: Pharmacovigilance requirements inspected and example findingsTGA Australia
Presentations given at the TGA information sessions cover the pharmacovigilance inspection guidelines, preparing for inspections, inspection process, and close out of inspections.
Online Clinical Trial Notification (CTN)TGA Australia
A brief overview of the clinical trials environment including the role of the Clinical Trial Jurisdictional Working Group and the Framework for Action (2) Provide an update on progress over the last year on key projects (3) Outline the importance of leadership and collaboration to maintain the momentum of improvements.
Presentation: The Australian Pharmacovigilance Inspection Program (PVIP)TGA Australia
Presentations given at the TGA information sessions cover the pharmacovigilance inspection guidelines, preparing for inspections, inspection process, and close out of inspections.
Presentation: Spotlight on prescription medicine post-market reformsTGA Australia
An overview of reform initiatives relevant to prescription medicines pharmacovigilance arising from the Review of Medicines and Medical Devices Regulation.
Presentation: Spotlight on prescription medicines reformsTGA Australia
An overview of initiatives arising from the Review of Medicines and Medical Devices Regulation relevant to prescription medicines as well as orphan drugs and developments for eCTD and the new MedSearch app.
Presentation: Pharmacovigilance requirements inspected and example findingsTGA Australia
Presentations given at the TGA information sessions cover the pharmacovigilance inspection guidelines, preparing for inspections, inspection process, and close out of inspections.
TGA Presentation: What’s happening in regulation?TGA Australia
This presentation provides an overview of the Government's response to the Expert Panel Review of Medicines and Medical Devices, with an emphasis on complementary medicines changes.
Presentation: Pharmacovigilance: The Australian landscapeTGA Australia
Overview of current post-market monitoring regulations and practice in Australia. Focusing on changing trends and the implications for future post-market vigilance practice.
Presentation: Conformity assessment evidenceTGA Australia
An overview of Conformity Assessment requirements and General Safety and Performance Requirements and demonstrating compliance in the Australian context.
Online Clinical Trial Notification (CTN)TGA Australia
This presentation provides a brief background on the TGA's role in the regulation of clinical trials as well as guidance on using the new online Clinical Trial Notification form
TGA presentation: Provisional approval pathway for prescription medicinesTGA Australia
This presentation provided an overview of some of the reform activities relevant to prescription, OTC and complementary medicines and implementation of recommendations from the Review of Medicines and Medical Devices Regulation including the content of the consultations on enhancements
Spotlight on MMDR Further Reviews and Advertising ReformsTGA Australia
An overview of reform initiatives relating to low risk therapeutic goods and the scheduling policy framework arising from the Review of Medicines and Medical Devices Regulation.
This presentation provides an overview of proposals for implementation of several reform initiatives relevant to prescription medicines, including expedited pathways for registration, enhanced post-market monitoring, variations to registered medicines, work sharing with comparable overseas regulators, the use of overseas assessment reports, and reforms to the orphan drug programs. The information session was held ahead of formal public consultations to provide an early view of the reform proposals to those stakeholders who will be most directly involved in the design of the new regulatory arrangements.
TGA Presentation: What’s happening in regulation?TGA Australia
This presentation provides an overview of the Government's response to the Expert Panel Review of Medicines and Medical Devices, with an emphasis on complementary medicines changes.
Presentation: Pharmacovigilance: The Australian landscapeTGA Australia
Overview of current post-market monitoring regulations and practice in Australia. Focusing on changing trends and the implications for future post-market vigilance practice.
Presentation: Conformity assessment evidenceTGA Australia
An overview of Conformity Assessment requirements and General Safety and Performance Requirements and demonstrating compliance in the Australian context.
Online Clinical Trial Notification (CTN)TGA Australia
This presentation provides a brief background on the TGA's role in the regulation of clinical trials as well as guidance on using the new online Clinical Trial Notification form
TGA presentation: Provisional approval pathway for prescription medicinesTGA Australia
This presentation provided an overview of some of the reform activities relevant to prescription, OTC and complementary medicines and implementation of recommendations from the Review of Medicines and Medical Devices Regulation including the content of the consultations on enhancements
Spotlight on MMDR Further Reviews and Advertising ReformsTGA Australia
An overview of reform initiatives relating to low risk therapeutic goods and the scheduling policy framework arising from the Review of Medicines and Medical Devices Regulation.
This presentation provides an overview of proposals for implementation of several reform initiatives relevant to prescription medicines, including expedited pathways for registration, enhanced post-market monitoring, variations to registered medicines, work sharing with comparable overseas regulators, the use of overseas assessment reports, and reforms to the orphan drug programs. The information session was held ahead of formal public consultations to provide an early view of the reform proposals to those stakeholders who will be most directly involved in the design of the new regulatory arrangements.
Good manufacturing practices for complementary medicinesTGA Australia
This presentation provides an overview of GMP clearance application process, the TGA compliance risk framework, major deficiencies and manufacturing quality challenges.
Biotechnology trends are explored in this presentation with a basic overview of laboratory procedures widely used in biotechnology, molecular genetics, immunology, and biochemistry. These are discussed in the context of broadly stated research objectives, the emphasis on applications and strategies rather than techniques and looking at what is influencing trends in Australia and overseas in areas covering cell biology, DNA, genes, mutations, proteins, RNA, plasmids, genetic engineering, biosimilars, stem cells, proteomics, antibodies, drug discovery, and drug development.
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.
Presentation: Regulatory affairs - The Australian and International landscapeTGA Australia
With local regulatory reforms and reactions to critical global events manifesting in more regulatory shifts, it has been hard to keep up with progress lately. This session provides an opportunity to hear directly from key regulators about their thoughts on the current and future regulatory environment and how it is evolving in response to these global shifts and the multitude of other challenges faced by regulators.
Expert review of medicines and medical devices regulation: Prescription medic...TGA Australia
This presentation outlines proposals for implementation of several recommendations from the Review of Medicines and Medical Devices Regulation relevant to prescription medicines, including expedited pathways for registration, enhanced post-market monitoring, variations to registered medicines, work sharing with comparable overseas regulators, and the use of overseas assessment reports.
Presentation: An Update on post-market regulatory requirementsTGA Australia
Along with implementation of expedited medicine registration pathways TGA has undertaken enhancements to its post-market monitoring of medicines, with a focus on assisting sponsors meet their regulatory requirements. TGA's new Pharmacovigilance Inspection Program (PVIP) involves interviewing sponsors and reviewing documents in order to assess sponsors' level of compliance with pharmacovigilance obligations. Work is also ongoing with sponsors to determine how best to confirm risk management plan (RMP) commitments are being met. This presentation will provide further detail on how TGA is working with and assisting sponsors satisfy their regulatory requirements.
201 regulatory aspects of drug and cosmetics .pdfBhavikaAPatel
regulatory aspects of drug and cosmetics
1. Regulatory Requirements for Registration of Drugs & Post Approval Requirements in WHO through Prequalification Program
2. FDA ORGANIZATION CHART
3. Marketing Authorization of EU for APPLICATION PROCEDURES
4. Global Countries Classification
5. Organization and structure of EMA&EDQMActive substance Master files IMPD
6. DRUG MASTER FILE in USA
Regulatory Update Panel
An overview of all Health Canada policies supporting access to Drugs for Rare Diseases, including regulatory pathways and support for innovation, patient engagement, Special Access Programs, aligned HC/CADTH/INESSS, international harmonization, post-market monitoring, support for patient registries, current status and relevance of biosimilars for rare disease patients
Rare Disease Day Conference 2020 March 9-10
This presentation covers the manufacture and testing of all sterile drug products, including drugs that are sterilized by filtration or other means and aseptically processed, and drug products that are terminally sterilized. The type of products covered include sterile bulk drugs, ophthalmic drugs, otic dosage forms, small volume parenteral (SVS) products for small molecule and licensed biological
therapeutic drug products, large volume parenteral (LVP) products, and any other drug products required to be sterile or labeled as sterile. Center for Biologics Evaluation and Research (CBER) regulated products and veterinary drug products are excluded from coverage under this program.
The guidance information is tailored to sterile manufacturing operations and should be used in conjunction with the Compliance Program for Drug Manufacturing Inspections (CP 7356.002).
Pharmacovigilance - a regulator's perspectiveTGA Australia
This presentation provides an overview of the TGA's Pre-market and Post-market pharmacovigilance methods. It describes the role and content of Risk Management Plans as well as adverse event reporting and signal detection and investigation.
Similar to The TGA Pharmacovigilance Inspection Pilot Program: 2015-2016 (20)
Pharmacovigilance and complementary medicines - Regulatory requirementsTGA Australia
Presentation on Pharmacovigilance basics – sponsor obligations, Complementary medicine safety – Regulatory perspective and Special considerations for complementary medicine pharmacovigilance
The challenges of regulating direct to consumer digital medical devicesTGA Australia
Presentation on digital medical devices, the role of the regulator, challenges in applying the framework to digital devices, international approaches and what is the TGA doing
Updates from the Pharmacovigilance and Special Access Branch TGA Australia
Presentation on using new sources of data in Pharmacovigilance, Pharmacovigilance Inspection Program (PVIP) update, International collaboration activities, Adverse Event Management System (AEMS)
Q and A
Manufacturing Investigational Medicinal Products - Legislative and GMP requir...TGA Australia
Presentation on Legislative requirements, specific risks for IMP manufacturing, manufacturing authorisations, PIC/S Guide to GMP PE009-13 and common issues
Update on regulatory reforms from the Scientific Evaluation BranchTGA Australia
Presentation on the latest on variations, Generic Medicines Reform Program, Human cells and tissue regulation (excluded goods), Faecal Microbiota Transplantation and 2D DataMatrix codes for medicines
Update on regulatory reforms from the Scientific Evaluation BranchTGA Australia
Presentation on the latest on variations, Generic Medicines Reform Program, Human cells and tissue regulation (excluded goods), Faecal Microbiota Transplantation and 2D DataMatrix codes for medicines
Presentation on the background of medicine shortages, definitions, reporting requirements, assessment and management, Section 19A and the compliance framework
Regulatory updates from the TGA Medical Devices Branch - Part 1TGA Australia
Presentation on the review of medicines and medical devices regulation, proposed changes to some definitions and regulation of some products without a medical purpose, reclassification of medical devices (not IVD), Unique Device Identification System and post-market monitoring
Regulatory updates from the TGA Medical Devices Branch - Part 2TGA Australia
Presentation on the regulation of software including software as a medical device, proposed regulatory scheme for personalised medical devices, including 3D Printed Devices, proposed changes to the Essential Principles, Conformity Assessment Procedures, and the requirements for devices used in clinical trials, and clarifying the requirements for systems and procedure packs
SME Assist: Help to navigate the regulatory mazeTGA Australia
Presentation to provide information on TGA’s SME Assist and what the service offers, details on upcoming SME Assist events and information on where to find more help
Presentation: Updates from the Pharmacovigilance and Special Access BranchTGA Australia
This presentation covers using new sources of data in Pharmacovigilance, Pharmacovigilance Inspection Program update, international collaboration activities and Adverse Event Management System.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Basavarajeeyam is a Sreshta Sangraha grantha (Compiled book ), written by Neelkanta kotturu Basavaraja Virachita. It contains 25 Prakaranas, First 24 Chapters related to Rogas& 25th to Rasadravyas.
Title: Sense of Smell
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 primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
DISSERTATION on NEW DRUG DISCOVERY AND DEVELOPMENT STAGES OF DRUG DISCOVERYNEHA GUPTA
The process of drug discovery and development is a complex and multi-step endeavor aimed at bringing new pharmaceutical drugs to market. It begins with identifying and validating a biological target, such as a protein, gene, or RNA, that is associated with a disease. This step involves understanding the target's role in the disease and confirming that modulating it can have therapeutic effects. The next stage, hit identification, employs high-throughput screening (HTS) and other methods to find compounds that interact with the target. Computational techniques may also be used to identify potential hits from large compound libraries.
Following hit identification, the hits are optimized to improve their efficacy, selectivity, and pharmacokinetic properties, resulting in lead compounds. These leads undergo further refinement to enhance their potency, reduce toxicity, and improve drug-like characteristics, creating drug candidates suitable for preclinical testing. In the preclinical development phase, drug candidates are tested in vitro (in cell cultures) and in vivo (in animal models) to evaluate their safety, efficacy, pharmacokinetics, and pharmacodynamics. Toxicology studies are conducted to assess potential risks.
Before clinical trials can begin, an Investigational New Drug (IND) application must be submitted to regulatory authorities. This application includes data from preclinical studies and plans for clinical trials. Clinical development involves human trials in three phases: Phase I tests the drug's safety and dosage in a small group of healthy volunteers, Phase II assesses the drug's efficacy and side effects in a larger group of patients with the target disease, and Phase III confirms the drug's efficacy and monitors adverse reactions in a large population, often compared to existing treatments.
After successful clinical trials, a New Drug Application (NDA) is submitted to regulatory authorities for approval, including all data from preclinical and clinical studies, as well as proposed labeling and manufacturing information. Regulatory authorities then review the NDA to ensure the drug is safe, effective, and of high quality, potentially requiring additional studies. Finally, after a drug is approved and marketed, it undergoes post-marketing surveillance, which includes continuous monitoring for long-term safety and effectiveness, pharmacovigilance, and reporting of any adverse effects.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
- Video recording of this lecture in English language: https://youtu.be/kqbnxVAZs-0
- Video recording of this lecture in Arabic language: https://youtu.be/SINlygW1Mpc
- 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
Muktapishti is a traditional Ayurvedic preparation made from Shoditha Mukta (Purified Pearl), is believed to help regulate thyroid function and reduce symptoms of hyperthyroidism due to its cooling and balancing properties. Clinical evidence on its efficacy remains limited, necessitating further research to validate its therapeutic benefits.
Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
The TGA Pharmacovigilance Inspection Pilot Program: 2015-2016
1. The TGA Pharmacovigilance Inspection Pilot Program
2015-2016
Mounir Mina
Manager, Pharmacist, Complementary Medicine and Medicine Problem Team
Signal Investigation Unit
Pharmacovigilance and Special Access Branch
ARCS Congress 11-12 May 2016
2. Overview
• Background to the pilot
• The sponsors involved
• The inspection process
• What was Inspected
• The Findings
• Common Deficiencies
• Feedback
• Next steps
The TGA Pharmacovigilance Inspection Pilot Program 1
3. Background to the pilot
• March 2015: TGA pilot program announcement, undertaking voluntary
pharmacovigilance inspections in Australia.
• May 2015: TGA dissemination of pilot information to industry for
expressions of interest.
• October 2015 - May 2016: 10 volunteer companies took part in the pilot
inspection program
The TGA Pharmacovigilance Inspection Pilot Program 2
4. The sponsors involved
• Aim: To inspect a variety of sponsors in order to understand the broad variations
in pharmacovigilance systems currently in place in Australia.
• Volunteers included:
– Large multinational companies
– Australian owned and based companies
– Smaller biotechnology companies
– Generic companies
– Complementary /herbal medicine companies
The TGA Pharmacovigilance Inspection Pilot Program 3
5. The Products Involved
• Registered Medicines
• Listed Medicines
• OTC
• Complementary
• Vaccines
• Innovative medicines
• Generic medicines
• Topical products
• Oral products
• Nasal delivery products
• IV products
• Medicines with RMPs/PSURS
• Medicines without RMPs/PSURs
The TGA Pharmacovigilance Inspection Pilot Program 4
6. The Inspection Process
Pre-Inspection
• Approximately one month prior to inspection a draft
agenda and initial document requests for the
inspection were sent to company.
• Several documents were requested to be provided
prior to inspection to allow for inspector preparation.
The TGA Pharmacovigilance Inspection Pilot Program 5
7. The Inspection Process
Inspection
• First day of the inspection: Opening meeting conducted to discuss the inspection process and
the background to the inspections and to allow for a company overview of the systems in place.
• Throughout the inspection:
– Interview sessions were conducted to gain an understanding in of the pharmacovigilance
processes undertaken by the company.
– Followed by document requests to verify/provide evidence of these company processes.
– In between interview sessions inspectors would review documents.
• Final day of the inspection: a verbal overview of any deficiencies identified during the inspection
was given to the company in the form of a closing meeting.
The TGA Pharmacovigilance Inspection Pilot Program 6
8. The Inspection Process
The TGA Pharmacovigilance Inspection Pilot Program
• Opening meeting conducted to discuss the inspection process and the
background to the inspections and to allow for a company overview of the
systems in place
First day of the
inspection
• Interview sessions were conducted to gain an understanding in of the
pharmacovigilance processes undertaken by the company
• Followed by document requests to verify/provide evidence of these
company processes
• In between interview sessions inspectors would review documents
Throughout
the inspection
• a verbal overview of any deficiencies identified during the inspection was
given to the company in the form of a closing meeting
Final day of the
inspection
7
9. The Inspection Process
Post-Inspection
• Four weeks after last document was received by the inspector, a formal
inspection report was provided to the company.
• The company then had four weeks to respond to the findings
– formal Corrective and Preventative Action (CAPA) plan (template provided)
– carry out any actions required
• The proposed CAPAs were assessed by the inspectors.
• Any changes or additions deemed necessary were negotiated.
• Once agreed by both parties, the inspection was closed out.
The TGA Pharmacovigilance Inspection Pilot Program 8
10. What was inspected?
1. ADR collection and processing
2. Processes for ongoing monitoring of safety
3. PSUR production and coordination
4. Maintenance of Reference Safety Information
5. The Australian person responsible for
pharmacovigilance
The TGA Pharmacovigilance Inspection Pilot Program 9
11. Relevant Legislation
During the inspection compliance with currently applicable Australian
pharmacovigilance regulations and guidelines was assessed:
• Therapeutic Goods Regulations 1990 (Regulation 15A)
• Therapeutic Goods Act 1989 (Section 28 (5e), 29A and 29AA)
• Australian requirements and recommendations for pharmacovigilance
responsibilities of sponsors of medicines (Version 1.3, June 2014)
• The Conditions‐ standard and specific applying to
registered or listed therapeutic goods
The TGA Pharmacovigilance Inspection Pilot Program 10
12. Grading of deficiencies
Critical Deficiency
• A deficiency in pharmacovigilance practice or process that has, or may significantly adversely affect the
safety or well-being of patients or that poses a potential risk to public health or that represents a serious
violation of applicable legislation and guidelines.
• Also occurs when it is observed that the sponsor has engaged in fraud, misrepresentation or falsification of
data.
Major Deficiency
• A deficiency in pharmacovigilance practice or process that could potentially adversely affect the safety or
well-being of patients or that could pose a potential risk to public health or that represents a significant
violation of applicable legislation and guidelines.
The TGA Pharmacovigilance Inspection Pilot Program 11
13. Grading of deficiencies
Other Deficiency
• A deficiency in pharmacovigilance practices or processes that cannot be classified as either critical or major,
but indicates a departure from good pharmacovigilance practice. Includes deficiencies that would not be
expected to adversely affect the safety or well-being of patients
• A deficiency may be “other” either because it is judged as minor, or because there is insufficient information
to classify it as major or critical.
The TGA Pharmacovigilance Inspection Pilot Program 12
14. The Findings
Number of findings:
• Critical findings - 0
• Major findings - 25
• Other findings - 18
0
5
10
15
20
25
30
Findings
Critical
Major
Other
The TGA Pharmacovigilance Inspection Pilot Program 13
15. The Findings
0 5 10 15 20
AE case collection and processing
Maintenance of RSI
Significant safety issues communication
Submission of PSURs
Ongoing monitoring processes
Deficiencies in procedural documentation
Australian PV person roles and
responsibilities
Critical
Major
Other
The TGA Pharmacovigilance Inspection Pilot Program 14
16. Some common deficiencies identified
AE case collection and processing
• Late submission and non-submission of serious Australian
cases to the TGA
– All serious adverse reactions occurring in Australia must be
reported to the TGA within 15 days of receipt by the sponsor
(Pharmacovigilance Guidelines).
• Non-conservative seriousness assessments
– Seriousness assessments should be an independent process to
medical evaluation, causality and validity of the case i.e. based
on the adverse event alone
– Where outcomes or treatment information is not available, a
conservative approach should always be taken
The TGA Pharmacovigilance Inspection Pilot Program 15
17. Some common deficiencies identified
AE case collection and processing
• Lack of due diligence in identification of AEs and special situation reports
– Care should always be taken to determine if an enquiry involves an adverse event for collection
and reporting purposes.
– Often relating to MI enquiry cases
• Deficiencies in the pharmacovigilance contracts and training of vendors
– Omissions, errors and discrepancies in contracts for post-marketing initiatives (e.g. patient
support programs and market research), sales, promotion and distribution partners.
– Contracts must ensure all safety information is collected and communicated to the sponsor
effectively; include provisions for reconciliation, training.
The TGA Pharmacovigilance Inspection Pilot Program 16
18. Some common deficiencies identified
Maintenance of Reference Safety Information
• Delays in updating Australian Product Information documents
– From when the sponsor became aware of the need to initiate a reference safety
change
– TGA expectation is a variation will be submitted within 6 months from
identification of any safety related issue
• Delays in updating product CMI documents
– CMI document needs to be changed within two weeks of the date of the
changed PI (Conditions of Registration)
The TGA Pharmacovigilance Inspection Pilot Program 17
19. Some common deficiencies identified
Communication of significant safety issues
• Deficiencies in communicating significant safety issues
– Sponsors must report all significant safety issues to the TGA within
72 hours (Pharmacovigilance Guidelines)
– Significant safety issues may include:
issues from review and analysis of AR reports occurring outside
Australia
action taken by a foreign regulatory agency
identification of new risk factors that may impact on the safety or
benefit-risk assessment of the product
The TGA Pharmacovigilance Inspection Pilot Program 18
20. Some common deficiencies identified
Submission of PSURs
• Schedule of PSUR submissions
– The intent of the Conditions of Registration is that PSURs cover periods aligning with the
Australian approval date i.e. first PSUR should cover a 6 or 12 month period from the date of
approval
– It is a requirement that sponsors request the condition to be varied if they are going to deviate
from this
– In several instances, PSURs submission timelines had been adjusted to align with international
birth dates without any formal approval to vary the conditions of registration
– The TGA is currently reviewing this requirement
The TGA Pharmacovigilance Inspection Pilot Program 19
21. TGA Feedback
• Pilot was an exercise to offer education and guidance to sponsors
– Foundation of TGA’s Regulatory Compliance Framework
• Examples of excellent pharmacovigilance processes in place
– Organised AR case collection and processing procedures
– Comprehensive ongoing monitoring processes
– Sufficient training of staff
• Commitment by companies to improve pharmacovigilance systems
The TGA Pharmacovigilance Inspection Pilot Program 20
22. Sponsor Feedback
• Participating companies were asked to fill out a questionnaire
– Regarding their experience of the inspection
– Will help shape any future program in Australia
• Responses on a whole have been positive:
– helpful in identification of areas in pharmacovigilance system
where improvement was needed
• time-consuming and challenges with time-zone differences.
The TGA Pharmacovigilance Inspection Pilot Program 21
23. Next Steps
To be determined…
• Feasibility of a national pharmacovigilance inspection program
• Any decisions and the implementation of an Australian program will involve an
industry consultative process.
• PV inspections will continue to use a risk-based approach that might include both
random and targeted inspections
• High level of sponsor compliance to good pharmacovigilance systems required
due to increased importance of post-market monitoring
The TGA Pharmacovigilance Inspection Pilot Program 22
24. Summary
• Background to the pilot
• Characteristics of sponsors who participated
• The Inspection Process
• What was inspected
• The findings
• Common deficiencies
• Feedback
• Next steps
The TGA Pharmacovigilance Inspection Pilot Program 23
March 2015: The TGA announced it would be undertaking a pilot program undertaking voluntary pharmacovigilance Inspections in Australia.
May 2015: the TGA disseminated information regarding the pilot to industry bodies in order to gain expressions of interest for pharmaceutical companies wanting to take part in the pilot.
October 2015 - May 2016: 10 volunteer companies took part in the pilot inspection program
Characteristics of the sponsors who participated
Volunteers were chosen to encompass both small companies and multinational companies, sponsors of complementary, over the counter and prescription medicines.
Opening Meeting: introductions, confirm purpose of inspection, discuss expectations, plan & methodology
Inspection is a combination of staff interviews and document reviews
Open dialogue from the beginning and ongoing verbal feedback throughout the inspection.
Studied specific examples to demonstrate the system
Verbal feedback of general findings at Closing Meeting
Opening Meeting: introductions, confirm purpose of inspection, discuss expectations, plan & methodology
Inspection is a combination of staff interviews and document reviews
Open dialogue from the beginning and ongoing verbal feedback throughout the inspection.
Studied specific examples to demonstrate the system
Verbal feedback of general findings at Closing Meeting
The collection and processing of spontaneous ADR reports (including sources of data, the role of medical information/product quality complaints, case receipt, case entry and quality assurance, follow-up, archiving and expedited reporting. As well as contracts with vendors/partners.)
The processes used to evaluate the ongoing risk-benefit profile of products (including ongoing monitoring activities: signal detection and evaluation, the management of risk management plans and the reporting of significant safety issues.)
PSUR production and coordination (Systems used to produce and submit PSURs to the TGA, including discussion of information included in the reports.)
Maintenance of Reference Safety Information (Overview of the management of variation requests (both sponsor and TGA initiated), process for the updating of Company Core Safety Information, PI and CMIs following the identification of new safety information and the implementation of PIs and CMIs following approval.)
The roles and responsibilities of the Australian person responsible for pharmacovigilance
Background quality systems including standard operating procedures and training were reviewed for each aspect of the pharmacovigilance system analysed.
Any non-compliances were deemed as deficiencies
Three types of deficiencies
Note: Classification of a deficiency is based on the assessed risk level and may vary depending on the nature of products.
Total number of findings for each type of deficiency identified in the Pilot Program
Findings broken down further…
(starting from bottom up)
AE case collection and processing- 19 findings (13 major, 6 other)
Maintenance of Reference Safety Information- 9 findings (8 major, 1 other)
Communication of significant safety issues- 2 findings (2 major)
Submission of PSURs- 5 findings (5 other)
Ongoing monitoring processes- 3 findings (2 major, 1 other)
Deficiencies in procedural documentation- 3 findings (3 other)
The roles and responsibilities of the Australian person responsible for pharmacovigilance- 2 findings (2 other)
15 days ADR reporting – mandatory as per PV guidelines (and Regulations)
Non-conservative - it is important that seriousness assessments are an independent process to medical evaluation, causality and validity of the case and be based on the adverse event alone. Where outcomes or treatment information is not available, a conservative approach should always be taken.
Care should always be taken to determine if an enquiry relating to a company product involves an adverse event that has occurred in a patient being treated with the product in question for collection and reporting purposes.
Often relating to Medical Information enquiry cases where AEs had not been identified or where reasonable steps to determine if an AE or special situation event, including off-label use had not occurred.
Contracts must ensure all safety information (including AEs and special situation reports) is collected and communicated to the sponsor effectively, that reconciliation of cases is described and there is provision for training in pharmacovigilance requirements. The company should have certainty that all safety information is being collected from such sources of data.
Significant delays in updating the Australian PI with newly identified safety information on a product are not acceptable and may pose a safety risk to the Australian public.
TGA expectation is a variation will be submitted within 6 months from identification of any safety related issue in order to ensure that the product information is kept up to date with the current scientific knowledge
“There is a continuing obligation to ensure that at all times the CMI complies with the statutory requirements; including consistency with the PI. If the related CMI document needs to be changed as a consequence of the change to the approved PI it must be lodged with the TGA within two weeks of the date of the changed PI.” (Conditions of registration for Australian medicinal products).
Significant safety issues may include issues identified following review and analysis of reports of ARs that have occurred in a country other than Australia, action taken by a foreign regulatory agency or identification of new risk factors that may impact on the safety or benefit-risk assessment of the product.
The conditions of registration for Australian medicinal products state that for PSUR submissions reports are to be provided annually, the annual submission may be made up of two PSURS each covering six months. The first report must be submitted to TGA no later than 15 calendar months after the date of the medicines approval letter. The subsequent reports must be submitted no less frequently than annually from the date of the first submitted report until the period covered by such reports is not less than three years from the date of this approval letter.
In several instances, PSURs had been submitted to the TGA as required however timeframes have been adjusted to align with international birth dates without any formal approval to vary the conditions of registration.
Note: TGA is planning to amend the condition to align PSUR submission with IBDs
This was a learning exercise for both the TGA and the companies involved. This pilot was an example of education, which forms the foundation for our regulatory work.
Unfortunately the report does not include details of the positive points observed during the inspection. We have also seen excellent examples of processes in place…
On the whole, we have seen a commitment by companies to improve pharmacovigilance systems.
Questionnaire responses are still being collected and analysed and will be used to assess the pilot and any future program in Australia.
Companies stated that they found the inspection helpful in identification of areas of the pharmacovigilance system where further improvement was needed and generally the process benefited the company in improving pharmacovigilance systems as a whole.
It was noted that companies did find the inspection, including lead up and follow on, to be time-consuming and that there were challenges in involving required international colleagues due to time differences.
Currently the pilot is still being completed, with CAPAs still being finalised and data collected.
The TGA will look at the feasibility of making this into a national program – any decision to do so and implementation of an Australian program will take time and will involve an industry consultative process.
Finally, Thank all those sponsors who volunteered and took part in the pilot.
Thank you for your attention.