Solid Oral Dosage Forms 6 Flashcards
What level of quality do we need from products?
Right product and strength Free from contamination No deterioration, no product breakdown In suitable correctly labelled container Protected from contamination and damage
Production of medicines: types of control
Reactive: take samples, at end then pass or fail
Pro-active: ensure product made right first time
Process Analytical Technology: better understanding of process, to give quality by design
Quality by Design, by latest FDA and EMEA initiatives: requires knowledge of design space in which acceptable products can be made
EU rules for pharmaceutical products, human and veterinary- orange book
Published by MHRA, Pharmaceutical Press I. MHRA II. GMP III. Legislation on manufacture IV. Guidance on wholesale distribution practice V. Legislation on wholesale distribution practice VI. Glossary of legislation VII. Index
Manufacturers Licenses
Standard provisions: what license holder needs to do- buildings, staff, organisation, documentation, GMP, rules
Undertakings for imported products: manufacturer must comply with holder’s product license- changes to building, staff, organisation, documentation, rules must be notified to license holder
QP must certify, if within EC/EEA can rely on manufacturer’s documents if outside must carry out full testing even if manufactured inside community
Qualified Person- releasing officer for medicines
In UK, science graduate and member of professional body
Assessed by panel on body of knowledge, and minimum 2 years experience
Collaboration with Medicines Control Agency and Veterinary Medicines Directorate
Professional code of practice
Qualification requirements for qualified person
Degree, diploma or formal qualification
Pharmacy, medicine, vet medicine, chemistry, biology
Acceptable after completion of university course recognised as equivalent by member state where studied
Course core subjects (qualified person)
Experimental physics, general and inorganic chemistry, analytical chemistry, pharmaceutical chemistry, general and applied medical biochemistry, physiology, microbiology, pharmacology, pharmaceutical technology, toxicology, pharmacognosy
How to become a QP
Need to have appropriate qualification
Experience working in industry, at least 2 years
Acquire the body of knowledge
Assessment by panel appointed by the professional bodies
Each professional body maintain registers
The body of knowledge
Candidate must demonstrate:
Relevant practical experience in one or more licensed product area
In-depth working knowledge and understanding, allied to practical experience
Thorough understanding of principles and requirements laid out in orange guide
Ability to translate those principles and requirements to other situations outside direct experience
Endorsement of credentials
Code of practice for qualified persons in the pharmaceutical industry
Operational guideline, functions within professional code of conduct
Routine duties ensures: compliance with marketing and manufacturing authorisation, clinical trials, human and vet medicines, including exports
Continuing professional development
Disciplinary procedures
Code of practice
Decline to act in release of products for which they do not have experience or knowledge
EIPG code of practice
QP should be satisfied medicinal products manufactured in accordance with GMP standards
QPs commitment to meet regularly with colleagues to understand contribution and impact on quality
Batch certification without adequate steps regarded as professional misconduct
EU guidance on manufacture
EC Guide to Good Manufacturing Practice
Marketing authorisations ensure all products assess by a competent authority
Manufacturing authorisations ensure that all products are manufactured by authorised manufacturers, who are regularly inspected
Covers human and veterinary meds
Quality management
Holder of a manufacturing license must: manufacture medicines fit for intended use, comply with marketing authorisation, not place patients at risk due to inadequate safety, quality or efficacy
Responsibility- senior management
Quality assurance
Everything that influences the quality of a medicine
It is the total sum of organised arrangements made with objective of ensuring that medicinal products are of quality required for their intended use
Incorporates GMP plus factors outside of the guide
Quality assurance- specifics
Takes into account GMP and GLP
Managerial, production and control operations are clearly specified
Correct starting and packaging materials
Controls on intermediate products and finished product
Qualified person certifies release
System for distribution of medicines to maintain quality
Self inspection/quality audit of QA system
GMP
All processes defined and reviewed
Critical processes and changes are validated
Necessary facilities, i.e. buildings, people, equipment etc.
Clear instructions, procedures and records
Trained people
Distribution and recall systems
Complaints handling and response
Quality control
Adequate facilities and trained staff
Sampling procedures for all stages
Validate test methods
Records to show what was tested and deviation from norm
Products comply with authorisation
Records to show no batch released without QP approval
Reference samples held
Product quality review
Periodic or rolling reviews of all licensed products to verify consistency of existing process, appropriateness of specifications, identity improvements
Reviews should normally be conducted annually
Personnel
Organisation with trained people- job descriptions, job responsibilities, personal records, system for delegation
Key people- heads of production and quality control
Who is responsible for quality- everybody
Training
Approved training materials Qualified instructors Records of qualifications Records of person's training Topics- GMP, QA, risks and contamination Visitors or untrained personnel entering production or quality control areas?
Personal hygiene
Medical examinations- infectious diseases or wounds and lesions
Protective clothing- 2 way, operator form product and vice versa
Working rules- hand washing, no food and personal medications in working areas, direct product contact should be avoided
Premises and equipment
Suitable for purpose- environmental conditions, design of building and work areas
Controlled access- authorised people, animals and other people
Key areas- production, QC, storage, ancillary, equipment and services
Equipment and area
Design- equipment and area suitable for tasks involved
Maintenance- planned activity to ensure equipment and area functions correctly
Monitoring- checking things are operating reliably
Documentation
Clearly written and legible
Types- specifications, instructions, procedures, records
Authorised and dated (retained for period of time)
Control of issue and replacement
Electronic data processing systems
Specifications
Starting and packaging materials, intermediate and bulk product, finished product Standards to meet, chemical and physical Sampling and testing methods Acceptance limits Storage conditions and shelf life
Manufacturing formula
Materials- name of product, description of form and strength, all starting materials to be used, quantities of all materials identified by standard names and codes, theoretical yield and limits
Processing instructions
Safety instructions
Location, equipment required and condition
Detailed step-wise process instruction
Expected yield
In-process controls
Bulk storage requirements, containers, labels, conditions
Packaging instruction
Name, product form and pack size All material and labels Safety instructions Process instructions In-process control
Batch processing records
Name of product Checks on equipment and area Dates, start and finish of each stage Initials of operator and verifier Batch numbers for all materials In-process controls Yield and limits
Production
General: supervision, handling, storage, labelling, checks, deviations
Prevention of cross contamination: segregation, layout, special cases e.g. penicillin
Validation
Materials: starting, packaging, finished product
Processing
SOPs
Clearly written and legible
Types: specifications, manufacturing formula, processing and packaging instructions, procedures, records
Authorised and dated
