10 golden rules

• Environment control

  Control air, water, lighting, ventilation, temperature, and humidity to ensure they do not impact product quality
• The Good Manufacturing Practice (GMP) regulations govern pharmaceutical and medical device manufacturing
• Facility layout


  The production area should be laid out to suit the sequence of operations to reduce chances of cross-contamination and avoid mix-ups and errors
• A logical and well-planned layout improves productivity by removing unnecessary traffic in the production area and segregating materials to minimize confusion and errors
• Use the '10 golden rules' to drive day-to-day operations with GMP implications
• The 10 golden rules of GMP

  • Get the facility design right from the start
  • Validate processes
  • Write good procedures and follow them
  • Identify who does what
  • Keep good records
  • Train and develop staff
  • Practice good hygiene
  • Maintain facilities and equipment
  • Build quality into the whole product lifecycle
  • Perform regular audits
• The white paper is an ideal refresher for experienced GMP professionals or great training material for newbies
• Every pharmaceutical and medical device manufacturer should aim to operate following the principles of GMP
• It's easier to be GMP compliant if the design and construction of facilities and equipment are right from the start
• Facilities should be designed to reduce the risk of contamination from the environment
• Before making changes, the company should have reviewed the layout as a whole
• Ensure equipment is easy to repair and maintain
• Ensure lighting, temperature, humidity, ventilation are appropriate and interior surfaces are smooth, easy to clean, and free from cracks
• Equipment should be designed, located, and maintained to suit its intended use
• Validation: '"A documented program that provides a high degree of assurance that a specific process, method or system will consistently produce a result meeting pre-determined acceptance criteria." [PE 009-14 Guide to Good Manufacturing Practice for Medicinal Products]'
• Validation is essential to ensure equipment and processes consistently perform as intended
• Validation Master Plan (VMP) preparation

  1. Company validation policy

  2. Validation roles and responsibilities

  3. Summary of facilities, equipment, systems, processes on site and their status

  4. Guidance on developing validation acceptance criteria

  5. Company validation (and re-validation) strategy
• Equipment requirements

  • Equipment should be designed, located, and maintained to suit its intended use
  • Easy to repair and maintain
  • Designed and installed in an area where it can be easily cleaned
  • Suitable for its intended use
  • Not reactive, additive, or absorptive
  • Calibrated at defined intervals (as necessary)
  • Clearly labelled
• Change control

  • Equipment or process must be subject to change control if a change to the validated state is required
  • Equipment, facilities, utilities, and systems should be evaluated at an appropriate frequency to confirm they remain in a state of control
• Validation activities

  1. Installation Qualification (IQ)

  2. Operational Qualification (OQ)

  3. Performance Qualification (PQ)
• Weak change control system

  Allowed changes to be made without formal evaluation and re-validation
• Documentation requirements in pharmaceutical and medical device industries

  • Specifications
  • Operating Instructions
  • Procedures
• Good documentation is an essential part of the quality assurance system and is key to operating in compliance with GMP requirements
• In the pharmaceutical and medical device industries, good procedures must be in place to ensure that processes are conducted in a controlled and consistent manner
• The oversight was due to a weak change control system that allowed changes to be made without formal evaluation and re-validation
• Golden Rule #3: 'Write good procedures and follow them'
• Specifications

  Detail the requirements with which products or materials have to conform, serving as a basis of quality evaluation
• Operating Instructions


  Detail material and equipment requirements and describe the steps to complete a task
• Procedures


  Give direction for performing certain tasks and provide higher-level instruction than operating (or work) instructions
• Writing good procedures

  • Procedures should be clear, concise, and logical
  • Outline tasks and create a brief breakdown of important steps and key points before writing
  • Use headings, tables, bullet points, and diagrams to make information easier to digest and follow
  • Visualise the user and use language they will understand
  • Increase readability by using simple sentences
• Ideas for improvement should be encouraged but the entire process should not be changed without conducting an impact assessment
• Each step in a procedure has been included for a purpose
• Shortcuts in following procedures may create pitfalls that can be costly
• Steps described in a written procedure should not be deviated from without approval
• It is a GMP requirement to regularly review documentation to ensure that it’s up to date
• Golden Rule #4: 'Identify who does what'
• All employees should clearly understand what they have to do each day to avoid misunderstandings and to minimise the risk to product quality
• The correct manufacture of medicinal products relies upon people
• Areas vulnerable to overlap in responsibilities include cleaning, validation, and calibration
• A job description should be created for each role to define job title, job objective, duties and responsibilities, and skill requirements