Lecture 3: Good manufacturing practice Flashcards
What defines medicine?
A drug with proved safety, efficacy and quality
When is a medicinal product fit for its purposes?
It is made to the correct formula, free from contamination has not deterioated it is in the right and properly sealed container It is correctly labelled
What does the manufacture of medicinal products need to comply with?
the drug regulatory and GMP requirements
to their specifications as outlined by the pharmacopoeias
When is good manufacturing practice used?
Used in the manufacture of medicines as a mean to enforce stringent and consistent product quality
What are the other good practices?
Good laboratory practice
Good distribution practice
Good clinical practice
What is GMP?
set of principles and procedures which help to ensure products manufactured will have the same required quality. These are followed in the manufacturing of therapeutic products
What is the basic principle of GMP?
quality must be built into each batch of product during all stages of the manufacturing process
What are the reasons for GMP?
A small number of defective products, or wrongly labelled items present in a batch can still be a very serious danger to patients.
Patients are not very good at detecting if there is anything wrong in the product so GMP must be employed
why is GMP sometimes referred to as cGMP?
cGMP = current GMP which indicates that manufacturers must employ technologies and systems which are up to date in order to comply with the regulation
Whenever the law is added or ammended it becomes the current GMP
What does GMP cover?
Plant Products People Processes Paperwork
What sort of GMP is incorporated in NZ?
the NZ code of GMP for manufacture and distribution of therapeutic goods.
Medsafe requires GMP certification for products regarded as medicines in NZ (even if NZ was not their country of manufacture.)
Which GMP certifications are recognised by Medsafe?
the member authorities of the PIC/S e.g. Australia therapeutic goods agency
US FDA
UK Medicines & Healthcare Products Regulatory Agency etc.
What is PIC/S?
Pharmaceutical inspection convention scheme.
This is a cooperative arrangement between health authorities in the field of GMP
What is the NZ code of GMP based on?
the PIC/S guide to GMP
What are the goals of PIC/S?
- mutual recognition of inspections
- harmonisation of GMP requirements
- Uniform inspection systems
- training of GMP inspectors
- Exchange of information and experience in the field of GMP and related areas.
What are the benefits of PIC/S membership?
Ensures all members comply with PIC/S standards
Allows cost savings due to PIC/S allowing shared GMP inspection reports
Facilitates exporting as PIC/S and non-PIC/S members affect GMP certificates from PIC/S participiating authorities
Enhanced market access and therefore enhanced sales
What are the NZ GMP guidelines?
quality management personnel premises and equipment documentation production quality control contract manufacture and analysis complaints and product recall self inspection
What are the main components of quality management?
quality assurance
GMP
quality control
What is quality assurance?
wide ranging concept covering all matters which influence the quality of a product.
The sum total of organised arrangements made with the objective of ensuring that medicinal products are of the quality required for their intended use.
What is GMP in terms of quality management?
GMP is the part of the quality assurance which ensures medicinal products are consistently produced and controlled to the quality standards appropriate to their intended use.
What are the two main things GMP is concerned with?
production
quality control
What is quality control?
the part of the GMP that involves sampling, specifications, testing, documenting and releasing procedures.
This ensures products are not released for use or sale until their quality has been judged to be satisfactory
What is good laboratory practice?
set of principles and procedures which when followed by lab studies, help ensure generate data can be used to assess hazards and risks
How are medicinal products manufacturered??
in a way that takes into account of the requirements of GMP and GLP
What are the requirements of Personnel in the NZ GMP guidelines?
An adequate number of personnel with necessary qualifications and practical experience are required.
Personnel responsibilities are to be clearly specified
The key personnels are to be (head of production and head of QC)
Training requires theory and practice of GMP for new staff
Peronnel hygiene is imperament. (procedures relating to health, hygiene practices and clothing of personnel)
What are the requirements of premises in the NZ GMP guidelines?
- Location and environment must present minimal risk of contaminating materials and products
- Flow of factory must be designed to prevent mix ups or cross contamination and entry of unauthorised people e.g. have defined areas for quarantine, rejected materials, released materials etc.
- Designed to permit effective cleaning and maintenance
- Constructed to suit the operations e.g. penicillins and cephalosporins in separate facility, herbal medicines, cytotoxics, steroids in required facilities.)
- Storage areas of sufficient capacity
- QC labs separated from production areas
What are the requirements for equipment under the NZ GMP guidelines?
- manufacturing/production equipment of GMP standard (high stainless steel grade)
- water piping/tank to be stainless steel (drinking water must meet WHO guidelines)
- Ventilation with computer control facilities (to allow adjustment of temperature, humidity, air filtration, air pressure etc)
- adequate lighting
What are the requirements for documentation under the NZ GMP guidelines?
-Documents need to be approved, signed and dated by authorised persons
What are the reasons for documentation?
prevents errors from spoken communication
keep records of what has been done
allow investigation upon complaint and defects etc.
What are the different types of documentation?
specifications (for starting and packaging materials and finished products) master/manufacturing formulae manufacturing & packaging instructions batch manufacturing & packaging records standard operating procedures
What do specifications do?
- serve as a basis for quality evaluation
- state the standards which materials and products should meet.
- describe tests which should be carried out to show compliance with these standards
When are specifications required?
written specs are required for
raw materials
packaging materials
finished products
What do the master formulae, manufacturing instructions and packaging instructions need to include?
name & amount of all starting materials used
(this includes ingredients which might disappear during processing) Batch size is also required
lay down all processing operations (equipment, mixing times, temperatures)
detail packaging operations (pack size, batch number, expiry date)
What are important things to adhere to regarding the master formulae, manufacturing instructions and packaging instructions?
an exact copy is issued every time a batch of product is going to be manufactured or packaged
these must be used and followed at all times
What do records do”?
provide a history of each batch of product
batch manufacturing records check the % product yield
batch production records check printed label/packaging reconciliation to ensure there are no discrepancies outside acceptable limits
How long should records be retained?
all records should be retained for at least 1 year after the expiry of the finished product
What are standard operating procedures?
These contain step by step instructions for carrying out a specific task
Who is responsible for the issuing and updating of SOPs?
the quality control unit which has autonomy and authority to act independently
What are the requirements with production operations under the NZ GMP guidelines?
production operations must
- follow clearly defined written procedures
- comply GMP principles
What are examples of production operatiosn complying with GMP principles?
- operations on diff products should not be carried out simultaneously in the same room (risk of mix up)
- validation is required (when there is any change in equipment, materials etc)
- starting materials (must be from approved suppliers and certified with CA)
- in process QCs should be carried out and recorded.
- packaging materials are to be issued by QC
- packaging operations should be adhered to
- finished products should be held in quarantine until release
- rejected products should be reprocessed or destroyed
- returned products should be destroyed, reused, or relabelled after being assessed by QC
What are examples of packaging operations which must comply with GMP principles?
diff products should not be packaged in close proximity
any unused batch printed labels should be destroyed and recorded
work area and packaging lines and printing machines need to be clean and free from any products or materials previously used
What are the main types of labels?
identity labels: indicate the product and what it contains
status labels: indicate stage of production progress (e.g. on test, quarantined, released, rejected
Finished product labels
When should labels be on products?
at all times during processing
All containers, equipments, rooms etc shuld be labelled
What should the identity and status labels contain?
name of material or product
batch number
date
What is quality control concerned with?
sampling, testing, specifications, lab validation (analytical methods) and release procedures
What are the responsibilities of QC?
products not released for use, sale or supply until their quality has been judged to be satisfactory
QC is not confined to lab operations but they ensure correct labelling, conduct stability studies, calibrate instruments, maintanence of equipments, attends to complaints.
independence from production (fundamental)
validated test methods
conduct annual product reviews (to verify the appropriateness of current specifications)
What are the factors involved with the finished product assessment?
production conditions
results of in process testing
review of manufacturing and packaging documentation
compliance with finished product specifications
examination of final finished pack
What is the principle of contract manufacture and analysis?
There is a written contract between the contract giver and the acceptor where the contract giver is the product license holder
for when someone wants to manufacture a medicine but does not have a manufacturing plant or equipment, they can employ a company to do it.
What happens with complaints and product recall?
Complaints concerning a product defect are recorded and reviewed thoroughly according to written procedures
recalled products should be identified and stored separately in a secure area while awaiting a decision on their fate.
What are examples of recalls in the UK in 2002/2003?
diazepam injection recalled due to visible particles
carbimazole 20mg tablets recalled due to less stated active dose
salbutamol 100ug inhaler recalled due to faulty valve resulting in 3-5x expected dose delivered
ditiazem 240mg capsules what arecalled for wrong packaging (packaged in 180mg blister packs)
What are examples of recalls in NZ (2010-2012?)
glucagen hypokit 1mg injection recalled due to cracking of glass vials
pacific atenolol 50mg and 100mg tabelts recalled due to variable doses of atenolol
BCG vacine 1.5mg powder for injection recalled due to sterility of vaccine not ensured
What are self inspections or internal audits?
These are where monitoring is in place to implement and comply with manufactring and control of procedures with GMP principles
These are usually conducted by the quality control unit
How are GMP failures classified?
critical
major
minor
What is a critical defect?
An observation if allowed to continue could cause serious harm and result in product recall.
These usually produce significant effects on purity, strength, identity or safety of product
e.g. cross contamination, incorrect labelling, active ingredients outside specifications
What is a major defect?
an observation if allowed to continue could lead to process failure, reduced usability or salability of a product but will not cause harm to the consumer
e.g. key equipment not calibrated
process deviations not properly documented or investigated
lack of SOP for equipment cleaning
What is a minor defect?
an observation of aesthetic or process neglect
These have a low probability of affecting the quality or usability of the product
e.g. cracks in wall surfaces
warehouse not cleaned according to schedule
sop review overdue
What is quality?
every product is fit for its intended use
What is the principle GMP is based on?
everything will be completely documentedq
What is the concept of GMP?
to ensure that the risks of making mistakes is reduced to a minimum
