The 10 Golden Rules of GMP in Pharmaceutical Manufacturing
What are the 10 golden rules?
Golden Rule #1
Get the facility design right from the start
Golden Rule #2
Validate your processes
Golden Rule #3
Write good procedures and follow them
Golden Rule #4
Identify who does what
Golden Rule #5
Keep good records
Golden Rule #6
Train and develop staff
Golden Rule #7
Practice good hygiene
Golden Rule #8
Maintain facilities and equipment
Golden Rule #9
Build quality into the whole product lifecycle
Golden Rule #10
Perform regular audits
Golden Rule #1
Get the facility design right from the start
Every food, drug, and medical device manufacturer aims to operate their business in accordance with the principles of Good Manufacturing Practice (GMP). It’s much easier to be GMP compliant if the design and construction of the facilities and equipment are right from the start. It’s important to embody GMP principles and use GMP to drive every decision.
Facility layout
Layout the production area to suit the sequence of operations. The aim is to reduce the chances of cross-contamination and to avoid mix-ups and errors. For example, don’t have final product passing through or near areas that contain intermediate products or raw materials.
A logical and well-planned layout will improve productivity. Sometimes you need to step back and reconsider the whole production area rather than applying quick fix solutions.
Aim to:
• remove unnecessary traffic in the production area which could result in a
hazardous environment
• segregate materials, products, and their components to minimise confusion
and potential for mix-ups and errors.
Example:
A company, through poor planning, failed to keep the product manufacturing process
linear. As the product moved through the factory, it was zigzagged from one area to
another. This meant that near-final product was exposed to early-stage product with
the potential of contamination. Before making any changes, the company should have
stepped back and reviewed the layout as a whole.
Golden Rule #2
Validate processes
It’s one thing to design and construct state of the art facilities and equipment, but how do you ensure that it’s operated in a controlled manner? This is where validation comes into play.
To prove that equipment and processes consistently do what they are supposed to do, testing and documentation is required. Consistent performance is the key to maintaining safety and effectiveness of every product and enhances a company’s reputation for quality and reliability.
Validation
By definition, validation is:
“Establishing documented evidence that provides a high degree of assurance that a specific process will consistently produce a product meeting its pre-determined specifications and quality attributes.”
It’s a GMP requirement to prove control of the critical aspects of certain operations. New facilities and equipment, as well as significant changes to existing systems, require validation.
All validation activities should be well-planned and clearly defined. This is usually using a Validation Master Plan, or VMP. Before you get to this stage consider all the critical parameters that may be affected and impact product quality; what happens if the stirring speed is changed? How does this affect temperature or pH? Once this is complete, define the testing and documentation required.
Validation usually involves:
• Installation Qualification, or IQ, which is testing to verify that the equipment is installed correctly
• Operational Qualification, or OQ, which is testing to verify that the equipment operates correctly
• Performance Qualification, or PQ, which is testing to verify that product can be consistently be produced to specification.
A protocol describing each test and the acceptance criteria should be prepared, and once the testing is complete, a report produced.
Change control
Once testing is complete and the equipment or process is known to be controlled, it’s important to maintain its ‘validated state’. Achieve this by correctly following written procedures, and properly maintaining and calibrating equipment. If a change to the validated state is required then it must be subject to change control.
A change control system should be in place to document all changes to facilities, equipment, or processes that may have an impact on product quality. You should evaluate the impact of the change and define the extent of re-validation.
Example:
A computer system was validated after it was first installed on site. Some years later an auditor discovered that changes had been made to the system. No re-validation work had been performed and the system was no longer in its validated state. How did the company know that the system was operating in a controlled and consistent manner?
The answer is they didn’t. The oversight was due to a weak change control system
Golden Rule #3
Write good procedures and follow them
Think about what happens in a workplace if written procedures are not available. People rely on longer-term employees to tell them how to do things and then do their job from memory. This is fine for a company making garden pots, but not so good when the products you are making can cause death!
In the food, drug and medical device industry it’s critical that good procedures are in place to ensure a controlled and consistent performance; it’s an essential part of GMP.
Procedures should be clear, concise, and logical. Consider hiring a professional technical writer to do the job. Unlike permanent employees they know how write well and will perform usability tests to ensure that documents work. Having an independent party reviewing your procedures also leads to process improvements
Documentation requirements
The following documents are typical in the food, drug, and medical device industry:
• Specifications: These detail the requirements with which products and materials have to conform, i.e. they serve as a basis of quality evaluation
• Operating Instructions: These detail material and equipment requirements and describe the steps to complete a task
• Operating Procedures: These give direction for performing certain tasks and provide higher-level instruction than operating instructions.
• Records: These provide a history of each batch and provide a mechanism to check that you are following operating procedures and instructions.
Writing good procedures
Outline the task before you begin writing the procedure. Create a brief breakdown of the important steps and key points related to the task; a flow chart is a useful tool. Remember that people don’t usually read procedures from start to finish; they tend to scan the document for keywords.
Break the procedure into chunks and use:
• headings
• tables
• bullet points
• diagrams.
This makes the information easier to digest and follow.
When writing procedures try to visualise the person that will use it. Use language they will understand and don’t include too much or too little information. You can increase the readability of your procedures by using simple sentences and by writing in a conversational style. Aim at a readability score that matches the educational level of the person using the document. You can also check that the procedure is usable by performing a ‘usability test’. Print out two copies of the procedure and ask someone unfamiliar with the task to follow it. Mark up the second copy with notes about where they found the document confusing. This will highlight problems with the document and is a great learning experience for the writer.
It is a GMP requirement to regularly review documentation to ensure that it’s up to date. Most companies have a three-year review cycle for their documents however this can be set according