Introduction to Good Manufacturing Practice

Rachel Bridson

Introduction

The key aim of any pharmaceutical manufacturing process is to produce a SAFE, PURE and EFFICACIOUS product

To ensure that this aim is met, quality assurance procedures must be in place

Definition of QA
..the sum total of the organised arrangements made with the object of ensuring that medicinal products are of the quality required for their intended use Directive 91/356/EEC

QA incorporates GMP and QC

QA

GMP
QC

Quality assurance (QA)

Production / control operations are clearly defined Managerial / team responsibilities are clearly defined Correct materials are used In-process controls and validation are carried out Finished product is correctly processed Storage and handling are appropriate Self-inspection and audit procedures exist

Definition of GMP
good manufacturing practice shall mean that part of quality assurance which ensures that products are consistently produced and controlled to the quality standards appropriate to their intended use.

You will often see cGMP current good manufacturing practice

GMP

Demands that: All critical steps within the process are defined and validated Only approved procedures are followed Detailed documentation is produced to ensure full traceability Overall objective is to ensure that the material consumed by the end user has the following defined attributes: Purity Strength Identity

GMP: Personnel

Should be competent, appropriately qualified and in sufficient numbers Everyone should have a clearly defined job description Hierarchical relationships should be shown on an organisational chart Initial and continuing training should be provided Personnel must follow established hygiene protocols

GMP: premises and equipment

Should be entirely suitable for the intended operations Lay out, design and operation must minimise risk of errors, cross-contamination and anything that may have an adverse effect on the product Premises and equipment that are critical for product quality will be validated (qualified)

Premises cont.
Each site will have its own unique constraints and problems: history neighbours security topography utility

access

generation and distribution transfers people materials information

GMP: documentation
Should be clear, up to date and accurate Must allow the history of each batch to be fully traced Should be retained for the specified period Data storage systems must validated and adequately backed-up

GMP: documentation system

EQUIPMENT VALIDATION PREPARATION CLEANING RECORDS PRODUCTION PRINCIPLES (SOP) RAW MATERIALS

SPECIFICATIONS REAGENTS
IN-PROCESS SAMPLES RECORDS AUDIT REPORTS

ENVIRONMENTAL MONITORING RECORDS

BATCH DOCUMENTATION

cGMP: production

All operations should be carried out according to pre-established instructions Process modifications must be validated Critical phases of the manufacturing process should be regularly re-validated Measures must be taken to avoid cross contamination and mix-ups Adequate and sufficient resources must be made available for in-process controls

GMP: Quality control

An independent QC department must be set up and placed under the control of a QP At least one, appropriately staffed and equipped lab must be available

Responsibilities of QC personnel
Monitor facilities for cleanliness Monitor manufacturing personnel hygiene Evaluate raw materials, packaging materials, intermediates and final product identity Perform product safety testing and final product release procedures

GMP: work contracted out

Must be subject to a written contract the contract acceptor must not then pass on work to a further party without written authorisation Contract must state all responsibilities and the manner in which those responsibilities will be met Contract acceptor must follow GMP and be subject to the necessary inspections

GMP: complaints and product recall

The manufacturer must have a procedure for recording and evaluating complaints An effective recall system should be in place The competent authority should be informed of any defects

GMP: self-inspection

As part of the QA system the manufacture must perform regular self-inspections to ensure that all guidelines and GMP principles are being followed Records should be kept of the results and subsequent corrective actions

Validation
Programme designed to identify, prove and document that your product consistently meets your specifications and quality attributes

it must be kept as simple as possible it must identify and deal with what is critical it must not validate what does not matter

Key Validation Issues

Formal

documentation is required
of performance factors

Consistency Measured

performance should meet pre-

set expectations

Validation types
Prospective

new facilities, equipment or products working process which can be used as benchmark historical performance data or observations

On-going

Retrospective

Validation Plan Contents

Introduction Brief introduction of plant or process Scope of validation Other plans? Responsibilities Objective Exactly what is to be achieved Process description Complete but concise description of all inputs, operations, outputs & limits Validation Matrix Extent of validation for each operation, service, item of equipment.. Acceptance Criteria Justified limits of acceptance

Validation Plan Contents

Procedures
Standard operating, analytical, cleaning, reporting... Format Format for all documentation Presentation of results People Specific training requirements packages Review & Approval Resources Estimate of manpower & equipment Preliminary schedule

Authorised signatures for protocol review & approval

Authorised signatures for plan review & approval

Cost of GMP ?
Difficult to quantify: it

is not the initial capital cost

it
it

is not the running cost

is the loss of business!

And finally.

Regulations are constantly developing

Pharmaceutical companies are increasingly outsourcing more of their manufacturing, research and clinical trial operations
Supply companies as well as pharmaceutical companies must embrace GMP to secure future business