Chapter 4
Legislation
and Standards
By the end of this chapter,
you will be able to:
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Name the key references
and guidance standards
in aseptic preparation
Define the term audit
Explain the differences between
licensed and unlicensed units
Explain what SOPs are and
give some examples
List other standards and
legislation used or followed
in your workplace
Introduction
In this chapter we are going to look at the
legislation and standards that control how we
work in aseptic production units to maintain
the highest quality standards.
Key References
Prompted by the thalidomide
tragedy in the 1960s, the
Medicines Act 1968 was brought
in to govern the manufacture and
supply of medicines in the UK.
The underlying principle of the
Medicines Act is that, subject to specified
exemptions, no medicinal product may be
placed on the market for sale, supply or offer
for sale without an appropriate marketing
authorisation (also sometimes called a
Product Licence).
The aim of the Act is to assure the quality,
safety and effectiveness of medicines and,
to a certain extent, place liability on the
marketing authorisation holder for adverse
effects arising from the use of their product.
Aseptic production units work to the standards
laid down in the Rules and Guidance for
Pharmaceutical Manufacturers and Distributors
(see current version). This is also
commonly known as the Orange
Guide, and its content as Good
Manufacturing Practice (GMP).
The standards in the Orange Guide
are compiled by the Medicines
Health products Regulatory
Agency (MHRA).
Chapter 4: Legislation and Standards
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Aseptic Processing
Edited by Alison Beaney
on behalf of the NHS
Pharmaceutical Quality Assurance
Committee, Quality Assurance
of Aseptic Preparation Services
(Yellow Guide) gives guidance on
all aspects of the principles of Good
Manufacturing Practice (GMP).
All aseptic preparation units
work to the standards set out
in Aseptic dispensing for NHS
Patients (Farwell Report). This
was produced in 1995 by John
Farwell and provides guidance
to NHS aseptic units on
standards of aseptic preparation.
Farwell (1995) sets out specific policies for
aseptic activity and highlights the need for a
quality system. These are observed in all units
and should include:
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Comprehensive quality assurance with
independent approval
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Reference to other legislative requirements,
where necessary, eg, COSHH, Ionising
Radiation Regulations, etc
Licensed Units
Some hospital manufacturing units hold a
Specials Licence granted by the MHRA. This
allows the unit to manufacture pharmaceutical
products without a product licence or marketing
authorisation that are required by industry.
Licensed units can:
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manufacture products and sell to external
customers;
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assign extended expiry dates to products,
provided they are supported by stability data.
Unlicensed Units
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Detailed, approved operational procedures
to cover all facets of the activity
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Defined responsibilities, competencies,
training and performance of staff involved
in the activity
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Control of all materials, including
containers, devices and packaging,
used in the processes.
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preparation is done by or under the
supervision of a pharmacist who takes full
responsibility for the quality of the product;
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Appropriate provision and use of special
clothing (for operator and product protection)
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the preparation uses closed systems
(i.e. not open to the atmosphere)
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Provision, maintenance and correct
performance of facilities and equipment,
including disposables, for the whole range
of activities carried out
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licensed sterile medicinal products are
used as ingredients or the ingredients are
manufactured sterile in licensed facilities;
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Consistent approach to product
presentation including labelling
products will be allocated a shelf life of
no more than one week and the shelf life
should be supported by stability data
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Full documentation of systems and
processes and other product-related issues,
e.g., customer complaints
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all activities should be in accordance
with defined NHS guidelines.
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Validation of all procedures
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Chapter 4: Legislation and Standards
Aseptic preparation units can operate
under an exemption from Section 10 of the
Medicines Act, when dispensing directly to
named patients. i.e. without a specials licence,
providing the following conditions are met:
Chapter 4
Legislation and Standards
Some differences between aseptic preparations under Section 10
Exemption, compared to specials manufacturing licence
Section 10 Exemption
Specials Manufacturing Licence
Maximum 7-day expiry
Expiry limited to stability evidence
Prepared or directly supervised by Pharmacist
Prepared by suitably trained person following
approved procedures
Must only be prepared against a legal
prescription
Can be prepared for stock
Final check and release may be done together
Final check and release MUST be done by
separate people
Release may be done by any locally approved
Pharmacist
Release may only be done by person
registered by MHRA, e.g. Pharmacist or
Qualified Person (QP)
Standards must comply with local and QA
regional audit
Standards must comply with MHRA
inspection which is much more stringent
Audits
Audits are a process of checks, carried out
to ensure that Good Manufacturing Practice
standards, such as those laid down in the Orange
Guide (see current version), Farwell(1995) and
PICS (2008) are upheld.
Licensed units are subject to inspection by
MHRA GMP inspectors every 2 years.
All units, both licensed and unlicensed, must
carry out regular internal and external audits.
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Internal audits should be carried out by
staff who are part of the management
organisational structure of the department.
Audits may be carried out internally according
to an audit calendar with action taken to
rectify any non-conformances as required.
External audits should be carried out by staff
who are not managerially accountable and are
independent of any service provision to the
unit. External audits should be carried out at a
suitable frequency, at least every 18 months,
as required by EL(97)52.
For Self Inspection, a self audit programme
should be established that monitors the
implementation and compliance with the
written guidelines for quality assurance
and good manufacturing practice, and
that considers the type and complexity of
operations performed, which includes:
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an annual self audit plan with records;
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evidence that adequate corrective actions
are undertaken.
Self audits should be conducted in an
independent and detailed way by designated
competent people.
Records of all auditing should be made,
with action plans compiled, completed
and re-assessed.
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Aseptic Processing
Standard Operating
Procedures (SOPs)
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Product sampling and testing
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Process validation
These are instructions and information on how
to carry out a wide range of operations in your
unit. SOPs are devised to ensure uniformity in
all processes and that the best way of carrying
out a task is determined and reproduced
consistently. SOPs should cover all areas
within the preparation process.
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Operation of the Unit
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Staff training and testing
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Request processing
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Action to be taken in case of system failure
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Controlled drugs
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Storage and distribution of products
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Spillage
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Product complaints and recalls
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Assembly and transfer of ingredients
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Laundry
These instructions should be followed at
all times with no deviation (unless under
exceptional circumstances where the deviation
is approved by a supervisor, has been
evaluated and documented and is known to
be safe and does not affect the quality of the
product in any way). No operator should rely
on word of mouth to transfer information and
there should be no individual interpretation
of information. If there is doubt about a
procedure or policy, the line manager should
be contacted and an explanation given.
Some examples are:
Other General Legislation
& Standards
Health and Safety at Work Act
The Health and Safety at Work Act 1974
identifies the Health and Safety responsibilities
of both the employer and the employees. Take
care of your own safety and that of others who
may be affected by what you do – your acts or
omissions.
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Management of procedures
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Error recording
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Cleaning and disinfecting
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Fridge validation
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Test failure
The purpose of the Health and Safety at Work
Act etc is to provide the legal framework
to promote, stimulate and encourage high
standards of health and safety at work.
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Unusual event recording
Further Reading
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Maintenance and repairs
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COSHH and Health & Safety
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Capacity and planning
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Entry and exit from facilities
You should read your department Health and
Safety procedures and be aware of risks to
yourself and others. Some considerations are
given below:
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Documentation
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Environmental monitoring
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Labels and labelling
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Use of equipment
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Waste
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Product preparation checks and release
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Chapter 4: Legislation and Standards
Control of Substances Hazardous to
Health (COSHH)
Using chemicals or other hazardous
substances at work can put people’s health at
risk, so the law requires employers to control
exposure to hazardous substances to prevent
ill health. Employers have to protect people
Chapter 4
Legislation and Standards
who may be exposed, by complying with the
Control of Substances Hazardous to Health
Regulations 1999 (COSHH).
✔
Know which is the right type of extinguisher
to use.
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Know where the fire exits are.
All places of work must be assessed to
establish the risks. You should refer to your
own local risk assessments and SOPs.
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Know where the fire alarm manual pushes
are in your area.
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Know the sound of the fire alarm.
Where possible, risks to health must be
reduced by use of alternative substances or by
the use of protective equipment.
DON’T
COSHH Data Sheets will be available for each
substance. These give details such as:
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Product Information
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Emergency and First Aid Procedures
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Health Hazard Information
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Effects of Exposure
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Handling and Storage
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Obstruct access to fire exits.
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Store items on top of fire extinguishers.
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Lock fire doors.
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Get changed from your cleanroom clothes
on exit – get out as soon as possible
IN THE EVENT OF A FIRE:
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Stop what you are doing. Leave it safe.
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Start to exit.
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Check adjacent rooms for other staff as
you exit.
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Do NOT get changed.
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Do NOT collect personal belongings.
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Leave unit by nearest appropriate exit. (Do
not use a ‘kick-panel’ if main exit is clear)
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Exit the Pharmacy by the most
appropriate exit.
Manual Handling
You should observe your organisations
procedures for lifting and handling, and should
receive appropriate training – follow your SOPs.
In production areas, special care should be
taken to check workstations and operator
positioning to reduce risks
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Check the positioning of your chair before
you start work
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Report to the senior member of staff for
roll-call AND report the unit clear.
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Avoid overstretching and twisting
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Take a break from repetitive movements at
reasonable intervals to avoid strain
DO NOT re-enter until advised by senior
member of staff.
Dealing with a Product Spillage
Fire Safety
Make sure you know what to do before you
find yourself confronted by a fire.
DO
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Know your fire instructions.
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Know where the fire extinguishers are in
your area, how to use the fire extinguishers/
organisations policy on their use
See Individual Product Data for Dealing
with Spillages.
You should:
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Minimise the number of people in the area
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Restrict access to the area
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For cytotoxics use a designated spill kit
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Be aware of your spillage SOP
Chapter 4: Legislation and Standards
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Aseptic Processing
Reporting of Accidents/incidents
For needle stick injuries
*Report all accidents/incidents immediately*
Individuals are expected to have a duty of care
when handling sharps, however injuries may
occur. Incidents should be reported on an
accident form. These may be assessed by a
senior person and action taken as necessary,
in accordance with departmental procedures.
All accidents/incidents in the work place
should be reported to a senior member of staff
and an incident form completed immediately,
detailing the incident and action taken.
First Aid
For accidental exposure to drug/cleaning agent
see relevant COSHH data sheet.
Task
There should be a copy of the Yellow Guide (Quality Assurance of Aseptic Preparation Services)
available in your unit. Read through Section 16 Internal and External Audits.
Make a note below of any additional points about audits that are relevant to your unit and you
should be aware of:
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Chapter 4: Legislation and Standards
Chapter 4
Legislation and Standards
Test Yourself
Write down as many examples of SOPs as you can remember (up to a maximum of 10).
Put a tick next to any that you have already followed/used or read in your day-to-day work.
Chapter 4: Legislation and Standards
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Aseptic Processing
Questions
Q1
How often should licensed units be inspected by MHRA inspectors?
(1)
Q2
Who should carry out external audits?
(2)
Q3
What type of audits must be carried out by unlicensed units?
(2)
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Chapter 4: Legislation and Standards
Chapter 4
Legislation and Standards
Q4
The following publications lay down the standards followed by all aseptic production
units. What names are commonly used to refer to them, and what is the purpose of
each publication?
Official name
Common name
Purpose
Aseptic dispensing for
NHS Patients
Rules and Guidance
for Pharmaceutical
Manufacturers and
Distributors
Quality Assurance of Aseptic
Preparation Services
(6)
Chapter 4: Legislation and Standards
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Aseptic Processing
Q5
What does COSHH stand for?
List 5 details that can be found on a COSHH datasheet
1.
2.
3.
4.
5.
(6)
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Chapter 4: Legislation and Standards