GMP module 01 - Quality Management Fundamentals
Outcome of the Module:
The basic concepts of Quality Assurance (QA), GMP and Quality Control (QC) are interrelated. The sum total of all these entities together comprises the pharmaceutical quality system (PQS). The functions or roles of QA, GMP, and QC are collectively critical to the effective and safe production and control of medicinal products.
On completion of this module, you will be able to:
- Recognize how attention to manufacturing a quality product reflects on day-to-day operations.
- Identity the role of Quality Assurance in pharmaceutical manufacturing
- Recognize how companies use GMP rules to minimize errors in manufacturing
- Identify the main roles and responsibilities of Quality Control
- Recognize the key elements of a pharmaceutical quality system
Part I: Quality Principles
Pharmaceutical products must be manufactured according to well-established GMP rules. These GMP rules have been developed over the last 50 years and are based on practical experience and accumulated knowledge in the industry.
A quality product refers to much more than one that simply passes its laboratory tests.
Everybody has a different understanding of the term “quality”. However, in the pharmaceutical industry, quality is very specifically defined. Quality is the sum total of a product’s purity, identity, effectiveness, and of course, its safety.
Products are expected to be pure, in that they must not contain any unapproved ingredients or any contaminants. If a product is not pure, it may have an adverse effect on a patient and would therefore become unsafe. An obvious example is bacteria in a sterile product.
GMP rules throughout manufacture of the ingredients and the product help us make a pure product.
Patients and healthcare professionals rely upon the labelling of a product to ensure that they take the right product and the right strength in the prescribed way.
Product labelling, if wrong, can significantly impact patient health and even cause death. GMP rules, particularly during the packaging steps, help prevent the product from being misidentified.
During clinical trials, products are verified that they “work”, or are effective. This is confirmed by regulatory agencies when products are approved for commercial manufacture.
Efficacy is largely affected by the amount of active ingredient in the product. For example, 100mg of aspirin is more effective than 50mg in most cases, so it’s important to formulate the exact amount only.
The product excipients (non-active chemicals) can also affect efficacy. For example, some drugs release slowly into the bloodstream due to the right excipients being present. If not, they might release too fast (a safety problem) or too slow (an efficacy/safety problem). GMP rules, particularly around the formulation and manufacturing steps, help to make an effective product.
Product safety is built into the product during its development cycle during non-clinical and clinical studies. In these phases, products are tested and investigated to see if they have unacceptable adverse effects on patients.
Manufacturers look for a range of “contra-indications” as well as the benefits of the product. During manufacture, it is possible to adversely impact the safety of a drug or biologic by, for example, mis-formulation, adding ingredients in the wrong order, or not following the exact manufacturing instructions. Changing the processing conditions or allowing product to degrade over the shelf life will impact product safety. Applying the GMP rules helps prevent loss of product safety.
Part II: Quality Assurance
One critical requirement of all drug manufacturers is that products can only be released to the marketplace if they meet all QC specifications, and they have been manufactured in accordance with the details approved by the government regulatory agency, and there have been no unresolved manufacturing errors.
The batch record provides the evidence and the assurance that the product is safe to release. The QA Department is required to independently oversee and review these activities.
QA is a wide-ranging concept that covers all matters affecting product quality. Each company may interpret its QA responsibilities slightly differently.
QA generally includes the oversight and management of:
- Compliance with government GMP regulations
- Documented procedures and GMP
- Control over starting materials
- In-process controls and validation
- QC testing of finished products
- Self-inspections I internal quality audits
- Release for sale
- Product reviews and trends
- Storage and distribution
The majority of incidents leading to defective drug products result not from failures In technology, but from human error or simple mistakes. The behavior, attitude, care, and knowledge of employees, therefore, are critical elements in manufacturing safe drug products.
The company is required to document procedures and GMP rules, but they have no value unless employees know and follow them in all their work practices.
Part III: Good Manufacturing Practice (GMP)
GMP rules have been developed over the last 50 years based on incidents, errors and disasters in drug manufacture. They represent an accumulated body of past experiences written down as rules, so that companies do not repeat past mistakes and put patients at risk.
GMP refers to a set or licensing requirements to which companies must adhere in order to obtain and retain a manufacturer’s license. GMP rules have been agreed upon by government and industry, and the rules have been gradually refined during over 50 years or experience in practice.
Internationally, GMP rules are referred to as codes, rules, or guidance to GMP. In the USA, GMP rules (also called current GMP or cGMP) are legally enforceable regulations. While the USA and international GMP are written differently, there is little difference in practice. The codes are written in a practical way to help manufacturers consistently make quality products.
Applying GMP correctly helps companies minimize errors during manufacture and packaging. GMP, then, always involves people, and the effects or their behavior during manufacture.
GMP requires personnel to document what they intend to do, to do what they intended, record what was actually done, and check the results against agreed specifications.
The GMP rules are there so companies do not learn by trial-and-error. Patients’ lives depend on pharmaceutical manufacturers not making mistakes.
Part IV: Quality Control
QC testing is only designed to test for product attributes that are well-known and understood. These attributes are part of the product specification. However, laboratory testing cannot pick up all defects because the test may not exist, the test may not be sensitive enough, or the test may not be required for that product.
Companies therefore have to rely upon GMP rules and QA systems to prevent these problems from occurring in the first place.
QC is the part of QA that checks the quality of a batch after it has been manufactured. QC verifies that ingredients and products meet written and approved standards, often called “specifications”.
The QC laboratory tests samples of raw materials and finished products. It is critical to get accurate results from QC tests. Otherwise, defective batches may be released and good batches may be rejected.
The role of the QC laboratory then, is to detect any possible defects once they have occurred, rather than prevent them from occurring in the first GMP Rules place. The QC laboratory’s specific responsibilities include: –
- Sampling, inspecting, and testing of starting materials and finished product
- Calculating and checking results against specifications
- Reporting all results and releasing on~ passed batches
Sampling of starting materials and finished products is completely governed by GMP regulations. All sampling procedures and plans must be documented.
If wrong or insufficient samples are taken or a poor sampling technique is used, any subsequent testing may then give misleading results. As a result, good product may be rejected, or much worse, defective product may be released.
Testing of samples in the laboratory is a mandatory requirement under GMP regulations. Its effectiveness, though, is limited because the entire batch cannot be tested nor can the batch be tested for all types of potential contamination.
In fact, QC testing is limited to looking for defects after they have occurred, so it is not a QA prevention system but rather a defect detection system.
Each product has a specific set of specifications registered with the government authorities. Starting materials and finished products are required to be tested to these specifications, and the results reported to QA management if there is a problem.
Batches may not be released to the market if results do not conform to the approved specifications.
Laboratory documentation and records must follow the same rules as manufacturing GMP documents. The QC lab is required to have SOPs, test methods, specifications, registers, logs and testing records in place.
These documents must be current approved, accurate, provide traceability and be archived for later review. Government auditors are particularly interested in the QC testing records when they conduct GMP audits.
Specifications are documented for starting materials, in-process product, and finished products. These specifications are submitted to the regulatory authorities when products are first registered. If specifications need to be altered for whatever reason, approval must be sought from the government regulators.
The finished product is required to meet the specifications throughout the full shelf life under the approved storage condition.
Each batch must conform to each specification when tested. All out-of-specification (OOS) conditions must be investigated.
Pharmacopoeias are legal standards for the quality of products and materials. They specify the quality attributes of products and materials in “monographs”, and provide information on how tests should be conducted.
Part V: Pharmaceutical Quality System (PQS)
The PQS places additional emphasis on the critical role management plays in ensuring product quality, compliance and effective process controls. Management provides leadership, and approves processes, systems and resources. They also take ultimate responsibility for the effectiveness of the QA. GMP and QC processes and procedures.
When product ownership changes, management should consider the complexity of this and ensure that the ongoing responsibilities are defined for each company involved and that the necessary information is transferred.
Management should ensure that resources are appropriately applied to a specific product process or site.
Senior management should ensure the quality objectives needed to implement the quality policy are defined and communicated. Performance indicators that measure progress against quality objectives should be established, monitored, communicated regularly and acted upon.
Pharmaceutical companies should plan and execute a system for the monitoring of process performance and product quality to ensure a state of control is maintained.
Senior management should establish a quality policy that describes the overall intentions and direction of the company related to quality.
Management should assess the conclusions of periodic reviews of process performance and product quality and of the PQS.
Senior management has the ultimate responsibility to ensure an effective PQS is in place to achieve the quality objectives, and that roles, responsibilities, and authorities are defined, communicated and implemented throughout the company.
Communication processes should ensure the appropriate and timely escalation of certain product quality and PQS issues.
The pharmaceutical quality system extends to the control and review of any outsourced activities and quality of purchased materials.
Conclusion:
Quality is everyone’s job, and it should pervade every aspect of pharmaceutical manufacture and packaging. Quality should not be tested into products, rather, it must be built in at each step or manufacture.
Quality manifests itself in not only obvious ways, such as during actual processing steps, but also in diverse areas such as in vendor assurance, personnel training, internal audits, change management, release for supply, and QC sampling.
Pharmaceutical manufacturers must integrate the key functions of quality control (which checks for defects after they have occurred) and regulations or GMP under the banner of quality assurance. QA is charged with preventing defects and errors from occurring by overseeing all aspects of producing a quality product.
Online Quiz:
- Number of questions: 10
- No time limit
- Allow you save and finish at a later date
- Allow you to go back and change your answer
- Attempting each question is mandatory
- Pass mark at and above 70%
- Print results and certificates