Cloudview Visual Networks

Transcription

Cloudview Visual Networks
Controlled processes in the
Pharmaceutical Industry
3DOM: changing how we view CCTV
The Cloudview Visual
Network System is a
web-based service
that has been developed to enhance the
availability and manageability of CCTV data
generated by analogue and IP CCTV cameras.
* Cloudview Visual Network Adapter needed
Cloudview®
Introduction
We all want to know that the drugs and medicines we take not only work, but are safe. That’s why the
Pharmaceutical Industry is one of the most tightly-regulated in the world and why it often takes more than
10 years for a new drug to get to market.
The regulatory bodies in each territory where a drug is sold want hard evidence from carefully planned and
monitored experiments before they’ll grant a license. And they’ll carry on checking for the side effects and
manufacturing quality of the drug once it’s being used. The chart below shows just how complex the process is.
Discovery Research
Basic Research
Synthesis
In-vitro Testing
Development Chemistry/Pharmacy
Bulk Rout
Assays
Stability
Scale-up
Formulation
Assays
Stability
Scale-up
GMP Batches
Clinical
Investigator's
Brochure
Pharma Screening
Secondary Pharma
Validation Batches
Data sheet
Clinical
Research
Regulatory Submission
Market Launch
Clinical Trial
Approvals
Clinical Phase IV
Preclinical Development
Clinical Phase
1
Bioanalytical
Extension
New Indication
PK/ADME
New Presentation
Toxicology
Clinical Phase
2
Clinical Phase
3
The whole process starts by trying to identify a New Chemical Entity (‘NCE’) that has some form of therapeutic
effect. The NCE must also undergo a range of safety tests to help avoid unwanted side effects. These two areas
- Lead Identification and Optimisation and Preclinical Development’- are subject to complex regulation and
compliance auditing known as Good Laboratory Practice (‘GLP’).
See Appendix 1 for further details.
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©2013 Cloudview Limited. Cloudview, Cloudview VNA and Cloudview VNS are registered trademarks
or trademark applications of Cloudview Limited. This document may be modified without notice.
It takes intensive work to establish how to manufacture large quantities of the active pharmaceutical ingredient ‘API’
and the finished tablet, capsule or injection – all within tight specifications. These specifications are applied at each
manufacturing stage so that every batch of the drug released meets strict standards for both quality and potency.
These elements, shown in the R&D illustration as ‘Development Chemistry/Pharmacy’ also include commercial
production and are subject to complex regulation and compliance auditing known as Good Manufacturing Practice
(‘GMP’) and Good Distribution Practice (‘GDP’).
See Appendices 2 and 3 for further details.
Testing NCEs on humans is, as you would expect, subject to strict regulation and requires approval from regulatory
authorities as well as Ethics Committees made up of both medical personnel and lay members. These clinical studies,
shown in the R&D illustration as ‘Clinical Research’, are subject to complex regulation and compliance auditing known
as Good Clinical Practice (‘GCP’).
See Appendix 4 for further details.
In order to apply for licenses to manufacture and sell the product all of the completed R&D studies – including raw data
and expert analyses – has to be submitted to regulatory authorities. These applications will contain huge amounts
of data gleaned from compliance audits undertaken by the applicant and the authorities. Nowadays this is submitted
digitally, but applications in the past could run to several tons of paper! So it’s not surprising that assessments by the
regulatory authorities and their independent experts can take up to a year.
Three-dimensional asset protection using
observational management
Products
The principles of 3DOM start by splitting assets into three groups: Property, People and Perception.
The people in each organisation work with the property at their disposal – including buildings, equipment and raw
materials – to create the processes that lead to products and services. The quality of the goods and services fosters a
wider public perception, which creates and supports the all-important brand.
The figure below demonstrates this, as well as the significance of patents, where a successful application can
guarantee 20-year commercial exclusivity in a territory for both processes and products.
Property
People
Processes
Perception
Products
Patents
Cloudview®
One system designed to help organisations to manage, monitor and protect their assets, including patents, is
Cloudview. This cloud-based visual network service enables users to create virtual networks of IP cameras that
transmit images via the Internet and then securely stores them on remote servers.
Quickly accessible from any smartphone, tablet or laptop, Cloudview enables users to quickly find, organize and
manage video footage. Customised alerts can also be set up and sent via email, SMS or MMS to designated contacts.
The best way to explain how Cloudview does this is to see how it applies to the stages identified in the process diagram
(figure 2) shown at the start of this Whitepaper.
Lead selection and optimisation
How drugs work
• Small molecules interfere with some process within the body. • Activity of the molecule depends upon its shape. • Pharmacological activity often blocks a process (eg local anaesthetics) or stimulates a process (eg heart drugs).
• Newer drugs can be proteins – very large molecules.
• Basic research starts with:
A new, or more complete understanding of some normal process within the body –
eg the development of a non-sedating antihistamine. A better understanding of how a condition develops when a process becomes abnormal –
eg the development of anti- inflammatory drugs for asthma.
3DOM Application:
• Video capture of laboratory activity could be used to support patent application and date of invention.
Lead selection
• Generally involves the development of a test that shows if a certain molecule has any effect.
• Testing of lots of compounds is called screening.
• High-throughput screening (‘HTS’) allows many thousands of chemicals to be tested.
• High quality compound libraries are very important for drug development.
3DOM Application:
Video capture of test procedures could be used to create Standard Operating Procedure (SOP). HTS often done by
contractors – 3DOM can be used to monitor if contractors follow SOPs.
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Medicinal chemistry
• Takes compounds that have activity and, using a rational approach, attempts to make them more potent.
• Synthesis and in vitro testing.
3DOM Application:
Often contracted out to specialist providers and so 3DOM can be used for video-capture of steps in synthetic route
for re-creation in house.
Lead optimization
• Pharmacological screening – testing the compound to confirm expected pharmacological activity.
• Secondary pharmacology - testing the compound for any unexpected pharmacological activity.
3DOM Application:
Often contracted out to specialist providers, so 3DOM can be used for video capture to support GLP compliance.
Preclinical Development
Bioanalytical
• The development of laboratory tests that can measure the amount of a new compound, or its breakdown products
(metabolites), in body fluids.
• An expensive and time-consuming process that begins once a compound has gone from ‘lead candidate’ to ‘drug
candidate’ status in the R&D pathway.
3DOM Application:
Video capture of sophisticated test procedures can support creation of training, SOP development and to support
GLP compliance.
Cloudview®
Toxicology
• Investigations to determine any obvious or potential toxic effects of the compound.
• Used to determine the likely ‘safe’ dosage range for a new compound.
3DOM Application:
Usually contracted out to specialist providers, so 3DOM can be used for video capture to support GLP compliance.
Pharmacokinetics (PK)
• Pharmacokinetics is the study of how rapidly a new drug is taken up by the body and removed from it.
• long ‘active’ levels remain in the bloodstream usually determines how often the drug must be administered in
humans (eg once or twice daily).
3DOM Application:
Often contracted out to specialist providers, so 3DOM can be used for video capture to support GLP compliance and
GCP compliance.
ADME
• How the body absorbs the compound.
• How the compound is distributed around the body.
• How the compound is metabolised .
• How the compound is excreted.
3DOM Application:
3DOM can be used for video capture to support GLP compliance, for GMP compliance (especially for radio-labelled
studies) and for GCP compliance in human studies.
Cloudview®
Development chemistry and pharmacy
Bulk material (API)
• The active pharmaceutical ingredient (API) that goes into the tablet or the injection.
• Need to develop a manufacturing route that will be capable of producing the API at the tonne scale.
• Need assays to test for purity etc. at each stage of the production process.
• Need to test for stability over time.
Finished drug product
• This is the term used to describe the formulation – perhaps a tablet, capsule or injection.
• Need to develop a manufacturing method capable of large-scale production.
• Need assays to test for purity etc. at each stage of the production process.
• Need to test for stability over time.
3DOM Application:
The manufacture and storage of ingredients from the supply chain can all be monitored by 3DOM. The manufacturing
route may be the subject of a patent which 3DOM video can support. The entire route comprises many steps and all
require GLP compliance plus comprehensive assay testing. 3DOM can be used to develop SOPs, train staff and monitor
GMP compliance. 3DOM video capture could form part of batch manufacturing records available for Qualified Person
(QP) release.
Good Manufacturing Practice (GMP)
•G
MP is a best-practice methodology applied to the manufacture of the API or the finished drug product in order
to meet industry standards and regulatory requirements.
• Production processes have to be carefully controlled to ensure that the quality, purity and potency of the
materials remain constant from batch to batch.
• The methodology involves lots of documentation, audits both internal and external and checks that could all be
supported by video capture.
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Clinical Research
Phase I trials
• First administration of the NCE to human subjects, mostly undertaken in Phase I Units similar to a
hospital setting.
• Trials normally limited to normal, healthy volunteers – usually males only – involving perhaps <100 people.
• The trials are primarily about safety and look to establish what happens after (i) single doses, (ii) multiple doses
and (iii) increasing doses.
Phase II trials
• These are essentially safety studies involving patients who have the disease/condition that the new drug is
intended to treat.
• May be undertaken in hospitals or in the community depending upon the disease/condition being studied.
• The trials do not normally seek to establish efficacy.
• May involve hundreds of patients but usually includes adults only and may exclude patients with
other conditions.
Phase III trials
• Very large studies that may involve thousands of patients. • Designed to establish that the new drug is both safe and effective. • Effectiveness may be assessed by comparison to placebo, to another active medication or both.
• Some Phase III studies may run over several years according to the disease/condition being studied.
3DOM Application:
Monitoring of GCP compliance; for example, video capture to confirm that volunteers or patients have each given
informed consent. Monitoring of GMP compliance when small batches of drug have been produced for studies.
Monitoring of activities within pharmacy to confirm correct medications have been prepared and supplied
for each person.
Onward monitoring of drug administration, assessment procedures and volunteer/patient responses – especially for
Phase I studies. Monitoring of laboratory procedures for SOP and GLP compliance – especially for
Phase I studies.
Monitoring of project management meetings as required – for example meetings where random codes are ‘unblinded’
or where adverse events are considered by medical staff.
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Conclusions
Understandably, the pharmaceutical industry is strictly regulated with laboratory, manufacturing and clinical
activities following Good Laboratory Practice (GLP), Good Manufacturing Practice (GMP) and Good Clinical
Practice (GCP) codes and legislation.
Regulatory approval to manufacture and market medicines hinges on substantial documentary submissions from
drug companies that (i) confirm the safety and efficacy of the new drug, (ii) confirm the ability of the company to
make batches of medicines consistently against tight release specifications and (iii) confirm that all of the studies
reported have been completed in full compliance with all regulatory requirements.
This compliance with regulatory requirements can be called into question in a number of ways and simply having
one manager ‘sign off’ what an employee has supposed to have done may be sub-optimal in certain situations –
particularly if issues arise later. The use of 3DOM offers a new and powerful tool that could serve to (i) underpin
confirmation of compliance and (ii) provide visual evidence for investigations that may arise in response to issues
that appear along the way. In addition, 3DOM provides cost-effective tools to capture processes as they happen
in real time. Such video capture can be used not only to monitor processes (either internally or at contractors’
facilities) but also to create SOPs and training programmes for other staff. It is likely that 3DOM could have
extensive utility in the pharmaceutical industry.
Cloudview®
Appendix 1: Good Laboratory Practice (“GLP”) - taken from MHRA website
Definition of Good Laboratory Practice
Good Laboratory Practice (GLP) embodies a set of principles that provides a framework within which studies are
planned, performed, monitored, recorded, reported and archived. These studies are undertaken to generate data by
which the hazards and risks to users, consumers and third parties, including the environment, can be assessed for
pharmaceuticals, agrochemicals, veterinary medicines, industrial chemicals, cosmetics, food and feed additives
and biocides. GLP helps assure regulatory authorities that the data submitted are a true reflection of the results
obtained during the study and can therefore be relied upon when making risk/safety assessments.
Requirement to comply with the principles of GLP
In the European Union and many other parts of the world it is a regulatory requirement that studies undertaken to
demonstrate the health or environmental safety of new chemical or biological substances should be conducted in
compliance with the principles of GLP. In the United Kingdom these requirements are contained within The Good
Laboratory Practice Regulations, Statutory Instrument 1999 No 3106 (external link), as amended by Statutory
Instrument 2004 No. 994: The Good Laboratory Practice (Codification Amendments Etc.) Regulations 2004
(external link). These regulations require that any test facility which conducts, or intends to conduct, regulatory
studies must be a member of the UK GLP Compliance Monitoring Programme. These regulations define a
‘regulatory study’ as a non-clinical experiment or set of experiments:
(a) in which an item is examined under laboratory conditions or in the environment in order to obtain data on its
properties or its safety (or both) with respect to human health, animal health or the environment
(b) the results of which are, or are intended, for submission to the appropriate regulatory authorities
(c) compliance with the principles of good laboratory practice is required in respect of that experiment or set
of experiments by the appropriate regulatory authorities (whether or not compliance with the said principles in
respect of that experiment or set of experiments is also a legislative requirement).
The UK Good Laboratory Practice Monitoring Authority
Responsibility for verification of adherence to the Principles of Good Laboratory Practice is a devolved matter, thus
the UK GLP Monitoring Authority (GLPMA) is a body consisting of the Secretary of State for Health, the National
Assembly for Wales, the Scottish Ministers and the Department of Health and Social Services for Northern Ireland.
Any one of the above acting alone or jointly may perform its functions. The UK GLP Monitoring Authority may
appoint such persons as they think necessary for the proper discharge of their functions. In practice the GLPMA
are a team based within the Inspection, Enforcement and Standards Division of the MHRA.
What does the GLPMA do?
The team performs a variety of inspections including compliance monitoring inspections, implementation
inspections of new facilities and may also perform audits of individual studies if this is requested by a receiving
authority. These study specific audits can take place either in the UK or abroad if work has been conducted in
a non-OECD member state. The UK GLP Monitoring Authority works to ISO 9002 and is audited by the British
Standards Institute. In addition to performing monitoring inspections of facilities within the GLP Compliance
Monitoring Programme, the GLPMA also perform inspections of contract GMP QC testing laboratories, GMP
QC Contract Laboratories and GCP for Clinical Laboratories. The Monitoring Authority formulates UK policy on
the interpretation of the Principles of Good Laboratory Practice and responds to enquiries from industry, other
government departments and other interested bodies in this regard.
International activities
The GLPMA represents the UK at a number of international forums concerned with the application of the
Principles of Good Laboratory Practice. As the Head of the UK GLPMA, Andrew Gray is a member of the OECD and
EC GLP working groups and as such provides a UK link to both organisations. The GLPMA has made significant
contributions to the OECD publications that interpret the Principles of Good Laboratory Practice and has actively
participated in efforts to harmonise inspection activities both in the EU and globally via the OECD.
Contacts for further information
If you have a question regarding GLP compliance in the UK, which is not answered by the information on these
web pages, you may send your question to the UK GLPMA general mailbox at: [email protected]
Introduction
The MHRA’s Good Manufacturing (GMP) Inspectorate is part of the Inspection Enforcement and Standards
Division of the MHRA. It assesses the compliance of organisations involved in the manufacture, import and
distribution of medicinal products. Inspections are performed to assess compliance with the conditions of the
relevant licence, the Medicines Act 1968 as amended, and European guidance on good manufacturing practice
and/or good distribution practice. This involves an assessment of personnel, premises, processes and procedures
to ensure the quality of the medicinal products manufactured / handled, would not be compromised.
What is Good Manufacturing Practice?
Good Manufacturing Practice (GMP) is that part of quality assurance which ensures that medicinal products are
consistently produced and controlled to the quality standards appropriate to their intended use and as required
by the marketing authorisation (MA) or product specification. GMP is concerned with both production
and quality control.
Our work
Inspections of UK sites are carried out whenever a company has applied for or been named on an appropriate
licence and periodically thereafter during the course of a licence. Additional inspections that may be required to be
performed are, for example, to follow up deficiencies raised previously, following reports of defective products, or
to follow up information received from external sources, for example “whistleblowers”. Applications to vary details
of the manufacturing authorisation may also trigger an inspection. Fees are charged for inspections and they
are conducted on a defined frequency in accordance with EU guidelines, unless circumstances dictate otherwise.
There is no legal requirement to notify the licence holder of an intention to visit and inspections may be
pre-notified or unannounced.
While the UK authorities do not issue manufacturer’s licences to overseas manufacturing sites supplying the
UK they are inspected when named on specific marketing authorisations. Overseas inspections focus on the
products to be imported, and the standards applied are the same as those applied in the UK. Additionally, sites
manufacturing Active Pharmaceutical Ingredients (API) are not issued manufacturer licences, but may be
inspected. Sites of manufacture of non-immunological veterinary medicinal products and storage sites for all
veterinary medicines are also inspected on behalf of the Veterinary Medicines Directorate (VMD) under the scope
of a Memorandum of Understanding between the MHRA and the VMD (37325Kb).
The GDP Inspectorate inspects a number of types of Wholesale Dealer companies, including both Human and
Veterinary products, full line and GSL only wholesalers. Additional information is available in our GDP section.
The GMP Inspectorate inspects a number of types of manufacturing companies, including, but not limited to:
• Manufacturers of sterile and non-sterile dosage forms.
• Manufacturers of ‘Specials’.
• Assembly - only sites.
• Assemblers of parallel imported products.
• Licensed hospital units including radiopharmacies.
• Medical gas manufacturers.
• Investigational Medicinal Products (IMP) for use in clinical trials.
• Active Pharmaceutical Ingredients (API).
• Biological medicinal products eg vaccines.
• Blood establishments and blood banks.
• Plasma collection and fractionation sites.
* Herbal medicinal product manufacturers.
• Medicines section.
• Importers of medicinal products.
• Contract testing laboratories.
External liaison
International co-operation has been an important part of the Inspectorate’s activities for many years. The UK
Medicines Inspectorate was a founder member of the Pharmaceutical Inspection Convention and is an active
participant in the Pharmaceutical Inspection Co-operation Scheme (PIC/S) (external link).
The GMP Inspectorate currently carries out regular inspections in a number of countries, including USA, India,
China and Japan both in connection with national requirements and on behalf of the European Medicines Agency
(EMEA) (external link), the World Health Organization (WHO) (external link) and the European Directorate for the
Quality of Medicines (EDQM) (external link).
For Community marketing authorisations, for example, licences granted under the centralised procedure, initial
inspection is carried out under contract to the EMEA. This is normally carried out by the Supervisory Authority
concerned, i.e. the Member State in which the product is to be made or imported. Subsequent inspections are
normally carried out routinely by the same authority although there is provision for one Member State to inspect in
non-Member States on behalf of another.
The EC negotiates Mutual Recognition Arrangements (MRAs) between the Community and third countries, which
include mutual recognition of standards of GMP and arrangements to ensure compliance by pharmaceutical
manufacturers. A current list of such agreements can be found on the EMEA website (external link). Under an
MRA, the Regulatory Authorities accept each other’s Inspection Reports and routine inspection by one authority of
manufacturers in the other’s territory is not required. In addition, the re-testing of imported products are normally
not required.
Consultative committee
The GMP/GDP Consultative Committee has two primary objectives:
(a) to advise and provide information to representatives of Professional and Trade Associations, the wider
Department of Health and Other Government Departments (OGDs) with respect to aspects of Good Manufacturing
Practice and Good Distribution Practice and the licensing of manufacturers and wholesale dealers.
(b) to provide a forum for consultation and discussion.
History
The Medicines Inspectorate was established within the Medicines Division of the Department of Health and
Social Security (DHSS) in 1971 in accordance with the Medicines Acts 1968 and 1971. It was set up to inspect
and ensure compliance with Standard Provisions (including GMP and GDP) by all applicants for, and holders of,
manufacturer’s and wholesale dealer’s licences in the UK. Over the next few years it absorbed the functions of
the Department of Health (DH) Inspectorate under the repealed Therapeutic Substances Act, which was only
concerned with biological products, and expanded to inspect manufacturers in other countries exporting products
to the UK. In 1975 inspections of NHS manufacturing units were begun at the behest of the then Secretary of
State for Health. With the removal of Crown Immunity in 1991 these units were required to hold licences and
became subject to statutory inspection. In April 1989 the MCA was established following the Cunliffe-Evans report
into the control of medicines. This brought two major changes. Firstly, the Agency was organised into multidisciplinary functional groups. This has gradually evolved over the years to reach the present organisation based
on pre- and post-licensing activities. The Inspectorate became part of the Inspection and Enforcement Division
responsible for inspection, licensing, testing and other activities associated with manufacture and distribution.
Secondly, the Agency was to be entirely funded by licence holders on the basis of user fees. In 1991 requirements
for manufacturing authorisations and GMP were harmonised within the European Community. The UK no longer
inspected or exchanged Pharmaceutical Inspection Convention (PIC) reports on manufacturers in other EC
Member States.
For questions related to the planning of inspections please contact [email protected] and for
general GMP/GDP questions please contact [email protected]
An email alerting service is also available for updates and new content on Good Manufacturing Practice.
Appendix 3: Good Distribution Practice (“GDP”) - taken from MHRA website
Introduction
The MHRA’s Good Distribution Practice (GDP) Inspectorate is part of the Inspections & Standards Division of the
MHRA. The GDP Inspectorate inspects such companies and their operations to verify their compliance with the EU
GDP guidelines: EU GDP guidelines. Companies which manufacture or wholesale medicinal products may only do
so if they hold the appropriate licence.
What is Good Distribution Practice (GDP)
Good Distribution Practice (GDP) is that part of quality assurance which ensures that products are consistently
stored, transported and handled under suitable condition as required by the marketing authorisation (MA) or
product specification.
Who are we?
The GDP Inspectorate has a team of inspectors based at the MHRA headquarters in London (151 Buckingham
Palace Road) and at two MHRA outstations (Welwyn Garden City and York).
What do we do?
Inspections of UK sites are carried out whenever a company has applied for or been named on an appropriate
licence and periodically thereafter during the course of a licence. Additional inspections that may be required to
be performed are, for example, to follow up deficiencies raised previously, following reports of defective products,
or to follow up information received from external sources, for example ‘whistleblowers’. Applications to vary
details of the manufacturing authorisation may also trigger an inspection. Fees are charged for inspections
and they are conducted on a defined frequency in accordance with EU guidelines, unless circumstances dictate
otherwise. There is no legal requirement to notify the licence holder of an intention to visit and inspections may be
pre-notified or unannounced. The Good Distribution Practice (GDP) Inspectorate inspects a number of types of
wholesale dealer companies, including both human and veterinary products, full line and General Sales List (GSL)
only wholesalers.
International liaison
International co-operation has been an important part of the Inspectorate’s activities for many years. The UK
Medicines Inspectorate was a founder member of the Pharmaceutical Inspection Convention and is an active
participant in the Pharmaceutical Inspection Cooperation Scheme (PIC/S) (external link).
History
The Medicines Inspectorate was established within the Medicines Division of the Department of Health and
Social Security (DHSS) in 1971 in accordance with the Medicines Acts 1968 and 1971. It was set up to inspect
and ensure compliance with Standard Provisions (including Good Manufacturing Practice and Good Distribution
Practice) by all applicants for, and holders of, Manufacturer’s and Wholesale Dealer’s Licences in the UK. Over
the next few years it absorbed the functions of the Department of Health (DH) Inspectorate under the repealed
Therapeutic Substances Act, which was only concerned with biological products, and expanded to inspect
manufacturers in other countries exporting products to the UK. In 1975 inspections of NHS manufacturing units
were begun at the behest of the then Secretary of State for Health. With the removal of Crown Immunity in these
units were required to hold licences and became subject to statutory inspection. In April 1989 the MCA was
established following the Cunliffe-Evans report into the control of medicines. This brought two major changes.
Firstly, the Agency was organised into multi-disciplinary functional groups. The Inspectorate became part of the
Inspection and Enforcement Division responsible for inspection, licensing, testing and other activities associated
with manufacture and distribution. Secondly, the Agency was to be entirely funded by licence holders on the
basis of user fees. In 1991 requirements for manufacturing authorisations and GMP were harmonised within the
European Community. The UK no longer inspected or exchanged Pharmaceutical Inspection Convention (PIC)
reports on manufacturers in other EC Member States.
For questions related to the planning of inspections please contact [email protected]
Appendix 4: Good Clinical Practice (“GCP”) - taken from MHRA website
Introduction
The MHRA’s Good Clinical Practice (GCP) Inspectorate is part of the Inspections & Standards Division of the
MHRA. It assesses the compliance of organisations conducting clinical trials using investigational medicinal
products with UK and EU legislation.
What is Good Clinical Practice (GCP)?
Definition from EU Directive 2001/20/EC, article 1, clause 2: “Good clinical practice is a set of internationally
recognised ethical and scientific quality requirements which must be observed for designing, conducting,
recording and reporting clinical trials that involve the participation of human subjects.” Compliance with this
good practice provides assurance that the rights, safety and well-being of trial subjects are protected, and that
the results of the clinical trials are credible and accurate. The principles of good clinical practice are outlined in
articles 2 to 5 in the EU Directive 2005/28/EC. ICH Topic E 6, the ICH Note for Guidance on Good Clinical Practice
is an international standard for GCP. It was adopted by the CPMP (CPMP/ICH/135/95) I July 1996 and became
operational in the European Union (EU) in January 1997. The ICH Note for Guidance on GCP replaced the previous
European Community GCP Guidelines, which were implemented in 1991.
What is the MHRA GCP Inspectorate?
In the UK, the GCP inspectorate is responsible for inspecting clinical trials for compliance with Good Clinical
Practice. Statutory Instrument 2004/1031 and subsequent amendment 2006/1928 provides the legal basis
for these inspections. This statutory instrument implements, in the UK, the EU Directive 2001/20/EC, “on the
approximation of the laws, regulations and administrative provisions of the Member States relating to the
implementation of Good Clinical Practice in the conduct of clinical trials on medicinal products for human use”
and the EU Directive 2005/28/EC, “laying down the principles and detailed guidelines for good clinical practice as
regards investigational medicinal products for human use, as well as the requirements for authorisation of the
manufacturing or importation of such products.” The GCP inspectorate consists of a team of GCP inspectors. By
conducting inspections at the sites of organisations conducting or involved in clinical trials, the GCP Inspectors
assess compliance with the requirements of legislation and guidelines relating to conduct of clinical trials involving
investigational medicinal product. Each Inspector has a statutory duty to assess compliance with medicines
legislation and holds a warrant accordingly.
What does the MHRA GCP Inspectorate do?
The function of the GCP Inspectorate is to assess the compliance of organisations with UK and EU legislation
relating to the conduct of clinical trials in investigational medicinal products. This is achieved through carrying
out inspections of sponsor organisations that hold clinical trial authorisations (CTA) or organisations that provide
services to clinical trial sponsors. These include pharmaceutical companies, contract research organisations,
non-commercial organisations such as universities, NHS Trusts and charities, investigational trial sites, clinical
laboratories, GCP archives and other facilities involved in clinical trial research. GCP inspections may also take
place following a referral, i.e., information received by the inspectorate relating to GCP non-compliance. The
MHRA GCP Inspectorate has participated in joint GCP inspections with inspectors from a number of EU Member
States. In addition, the GCP Inspectorate has been instrumental in providing advice and training to GCP inspectors
from countries within and outside the EU. GCP Inspectors also shadow inspections conducted in the UK by foreign
agencies; eg the American FDA and the Japanese Ministry of Health & Welfare.
What rights do GCP Inspectors have?
Inspectors have rights conferred under the Medicines Act sections 111(1 to 3) and 112 (1 to 4 and 7) as well as
subordinate legislation applying the Act, primarily the Statutory Instrument 2004:1031 The Medicines for Human
Use (Clinical Trials) regulations 2004. These include the right to enter any premises involved in clinical trials
of investigational medicinal products to carry out inspections, take samples, require the production of books
and documents, and to take copies of, or copies of entries in, such books and document and seize and detain
substances, articles and documents. It is a criminal offence under section 114 (2 and 3) of the Medicines Act 1968
to obstruct an Inspector during the conduct of an inspection covered by the Act.
Phase I Accreditation Scheme
Following the TGN1412 incident in March 2006, where six clinical trial subjects became seriously ill and were
admitted to intensive care, an Expert Scientific Group (ESG) was formed to review Phase I clinical trials. One of
the recommendations from the ESG was to establish a national accreditation system for First in Human (FIH)
studies. The MHRA have developed such a scheme in order to maximise subject safety and to create additional
public confidence in the regulatory oversight of such trials. The development of the scheme has involved wide
consultation with representatives from industry associations, academia, NHS, Department of Health, Ethics
Committees, the Faculty of Pharmaceutical Medicine and the UK Resuscitation Council.
In addition, the opinion of the Commission on Human Medicines (CHM) and also the Expert Advisory Group of the
CHM has been sought. A public consultation exercise (MLX 341) took place which ended on 12 October 2007.
The proposal has been revised to reflect these comments and we are now in a position to implement the scheme.
We also plan to reconvene the consultative committee to review the scheme approximately six months
following implementation.
External links
(The MHRA is not responsible for the content of external internet sites.)
• Statutory Instrument 2004:1031 The Medicines for Human Use (Clinical Trials) Regulations 2004
• Statutory Instrument 2006:1928 The Medicines for Human Use (Clinical Trials) Amendment Regulations 2006
• Statutory Instruments
• Explanatory Memorandum
• Statutory Instrument 2006:2984 The Medicines for Human Use (Clinical Trials) Amendment (No. 2) Regulations
2006
• Statutory Instruments
• Explanatory Notes
• EU Directive 2001/20/EC
• EU Directive 2005/28/EC
• The Rules Governing Medicinal Products in the European Union: Volume 10 Clinical Trials
• ICH GCP (pdf file)
• Clinical Trial Tool Kit
•National Research Ethics Service (NRES)
•ICH
Contact for further information
For further information on this part of our site, please contact either:
1. GCP Inspectorate, MHRA, 151 Buckingham Palace Road, Victoria, London SW1W 9SZ ,
telephone 020 3080 6000.
2. GCP Inspectorate, MHRA, 2 Falcon Way, Shire Park, Welwyn Garden City, Hertfordshire, AL7 1TW,
telephone 01707299130, fax 01707 376649.
3. GCP Inspectorate, MHRA, 2a Hunter House, 57 Goodramgate, York, YO1 7FX,
telephone 01904 610556, fax 01904 625430.
4. Email [email protected]
5. [email protected]

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