Good Manufacturing Practices for Quality Assurance in the Lab

This document serves to clarify the crucial systems found in Quality Assurance Systems including, but not limited to GMP practices.

by Jeff Wu - Oct 4, 2022

Abstract / Summary

This document serves to clarify the crucial systems found in Quality Assurance Systems including, but not limited to Good Manufacturing Practices (GMP) in the lab.

Definitions

  • Quality Assurance (QA) – establishes and maintains requirements for manufacturing consistent products. 
  • Quality Control (QC) – Sometimes interchangeable with QA, it is actually a part of a QA program used to control and sometimes test product output.
  • Quality Management System (QMS) – formalized system that documents processes, procedures, and responsibilities for achieving quality policies and objectives. The purpose of which is to ensure that every time a process is performed, the same information, methods, skills and controls are used and applied in a consistent manner.

  • Good Manufacturing Practices (GMP) – covers all aspects of production from the starting materials, premises, and equipment to the training and personal hygiene of staff. Detailed written procedures (SOPs) are essential.
  • Standard Operating Procedures  (SOP) –  are used to lay out operations consistently and repeatedly in the same repetitive manner. 
  • Deviation – a departure from, or non-fulfillment of, a documented instruction.

Quality Assurance

QA Through Time

    1. Origin

      1. QA practices became more important in the United States during World War II, when high volumes of products had to be produced and inspected.
      2. In 1941 nearly 300 people were killed or injured by one company’s sulfathiazole tablets. That incident caused the FDA to revise manufacturing and quality control requirements, leading to what would later be called GMPs.

    2. Relevance today and for the company

      1. Utilized the knowledge of labs across the world to avoid errors, hazards, and poor product output.
      2. Encourages collaboration, establishes ownership.
        1. Everyone works together to create a document that reflects the process, and everyone knows who to ask questions about the process.
      3. Sets a high standard.
        1. Documented processes often create more consistent and higher quality products because the best process is identified and repeated.

  2. Important Points

    1. Consistency

      1. Consistent products minimize rejection. Consistency can be achieved with tools like:
        1. Data
        2. Standards and Procedures
        3. Passionate employees
        4. Quality Audits

    2. Quality Control

      1. QC creates a system to check products the same way every time, so the customer is receiving the same product every time.

    3. Safety

      1. Working environment, production methods, employee collaboration, feedback, and process improvement are prioritized in QMS-lead environments.

    4. Effectiveness

      1. If a process doesn’t work, it can be quickly identified and improved with documented step-by-step SOPs.
      2. New hires can be quickly trained and utilize the reference material to learn the process quickly and avoid “tribal knowledge”.

  3. Documentation

    1. Tribal Knowledge

      1. Tribal Knowledge is knowledge, information, experiences, and skills about processes that are generally translated audibly and not written down.
      2. Ex: John has been processing this product for 5 years, and has a lot of tips and tricks to help the process go smoother. These things are not written down, and you can only learn them by working one-on-one with John.
      3. When utilized correctly, via writing the information down in a document, it can keep organizations afloat through shift changes, vacations, retirement, etc.
      4. If a group has a lot of tribal knowledge and a lack of written instruction, this could indicate gaps in onboarding, process improvement, and training.

    2. Tracing process improvement

      1. Tracking process improvement uses the current business strategy to drive improvement. Tracking can include:
        1. Developing tools
        2. Identify problem areas
        3. Measure performance
        4. Validate change
        5. Creating models of current and future processes
      2. Tracking can be recorded on the following records:
        1. Spreadsheets
        2. Logs
        3. Forms
        4. Batch records
        5. NR/CAR/CAPA forms
        6. Employee metric sheets
        7. Software input
      3. The more metrics there are, the more data there is to work with the track improvement and identify early if a change is ineffective or a process needs improvement.

  4. Records

    1. Deviations and Corrections

      1. Deviations can be defined as a departure from a document instruction. When the departure can or does affect the end product, it is important to understand why it happened and how to prevent it from happening again. Deviations that are performed but solved within a group of one or two people can benefit other operators greatly, but only if the information is shared. Recording deviations are beneficial to not only the individual user, but the company, process, and product.
      2. Corrections are a documented process, sometimes only a sentence or two, to fix or improve a deviation. Sometimes this will make a product or action acceptable for use or release. Corrections are generally quick and for small deviations.
      3. Repeated corrections can lead to more lengthy investigations, with the end goal usually always aiming to improve a process, outcome, document, or training.

    2. Traceability

      1. Traceability is defined as the process of recording necessary information which is then tracked in business processes. It is used to ensure that a product’s exact history can be tracked if the need ever arises.
      2. Traceability is widely utilized for minimizing damages, improving management challenges, preventing serious recall problems, and keeping up with industry compliance.
      3. Lot Numbers and Batching
        1. A lot number is a unique identifying system (generally numbers, sometimes a combination of letters and numbers) assigned to one ingredient or material.
          1. Ex. LOT # B-01580609 means that the product was manufactured on February 15, 2008, and the earliest expiration date for any item in the kit is June, 2009.
            Lot Numbers and Batching graphic 1Lot Numbers and Batching graphic 2

      4. Ingredients or Raw Material

        1. All ingredients and materials used in products should be assigned lot numbers when they are received. A unique lot number must be assigned to each incoming shipment.
        2. The lot numbers must be traced through the manufacturing process and tied to each batch in which the lot is used.

      5. Sampling

        1. Sampling is the selection (gathering) of a representative portion of the population to make inferences about the entire population.
        2. It is important to gather samples at regular intervals in the process rather than at one time, such as at the beginning, middle or end.
          1. Example: If a product is manufactured for 6 hours, it would be beneficial to collect a sample after 1 hour, 3 hours, and 5 hours.
          2. Scenario: If a temperature-sensitive product is manufactured for 6 hours, and the room temperature changes significantly around noon, collecting all of the samples at noon does not accurately depict the product before the temperature change, during the temperature change, and after.
        3. Sampling is often used for QC testing to ensure the product meets internal or regulatory standards.

  5. Building and Facilities

    1. Size, lighting, ventilation, and safety

      1. Safety is a high priority in both Quality and GMP certifications. Buildings and facilities should provide adequate resources for all employees to safely carry out their tasks. Unsafe environments should be reported to management for process improvement.
      2. Ventilation should be prioritized for volatile and gaseous chemicals and products. Fume hoods should be regularly inspected to ensure adequate function, and proper technique (closing the vent hood glass to the proper level, not leaning into vent hood during use, etc) should be trained periodically to ensure all operators are adequately protected.

  6. Equipment

    1. Cleaning

      1. Equipment should be cleaned prior to use, and regular cleaning and maintenance should be utilized, recorded, and scheduled.
      2. Never assume an item is safe to clean in the sink with soap and water. Use cleaning agents described in documentation or operator manuals.
      3. Always use a cleaning SOP when available, and ask management if unsure of how to clean a device.

    2. Maintenance

      1. Regular maintenance ensures equipment is working within the intended range, value, or function in which it was intended.
      2. Preventative Maintenance (PM) is regular, planned maintenance that is scheduled according to usage or time-based triggers. The purpose of PM is to lessen the likelihood of equipment breakdowns.
      3. Equipment with spills, broken parts, or malfunctions should be tagged “Do Not Use” until the proper personnel are able to correct the issue. This helps avoid further damage to the equipment.

    3. Calibrating

      1. Calibration maintains accuracy, standardization and repeatability in measurements, assuring reliable benchmarks and results. Without regular calibration, equipment can fall out of spec, provide inaccurate measurements and threaten quality, safety and equipment longevity.

  7. Personel

    1. Education/training

      1. Lack of education/training can make products unsafe— it can also lead to serious problems with regulatory bodies.
      2. Training should be repeated at regular intervals (annually, bi-annually, etc.) to ensure all staff are up-to-date on any changes or updates to the process.
      3. Training should be recorded, and those records stored and maintained.

    2. Clothes and PPE

      1. Protective Equipment (PPE) includes safety glasses, goggles, face shields, gloves, lab coats, aprons, ear plugs, and respirators. Personal protective equipment is carefully selected to ensure that it is compatible with the chemicals and the process used.
      2. Proper attire is essential in the lab. There is always a chance of contacting a chemical spill or a sharp edge on a piece of equipment.
      3. Wear long pants or skirts and closed toed shoes, and tie back long hair. Do not wear shorts, short skirts, sandals, loose clothing, or dangling jewelry.
      4. Ensure that clothing covers and protects from spilled chemical, biological, or radioactive materials, falling objects, and other lab hazards.

    3. Food and Beverages

      1. The OSHA Lab Standard prohibits eating/drinking in areas where hazardous chemicals are in use.
      2. Personal safety risks can result from cross-contamination and ingestion. Contamination can result from contact with contaminated gloves/hands, airborne materials settling out or condensing on surfaces or utensils, or placing consumable items on a contaminated surface.

    4. Visitors

      1. Visitors to labs are generally escorted while on the property. Many labs are locked and access may only be granted with a key card or code.
      2. Visitors are discouraged from areas with hazardous materials.
      3. A visitor log is beneficial to help screen visitors, from clients to interviewees. More sophisticated visitor management systems can also assign different levels of access to various types of visitors.

  8. Water

    1. Quality

      1. Heavy metal and impurity contamination is a concern for manufactured products, especially if water is used frequently.
      2. ICH Q3D states “The risk of inclusion of elemental impurities from water can be reduced by complying with compendia (e.g., European Pharmacopoeia, Japanese Pharmacopoeia, US Pharmacopeial Convention) water quality requirements, if purified water or water for injection is used in the process.”
        Water quality image
      3. As long as no significant changes to the quality of the water supply to the site occur, it is unlikely that the purification process supporting the claim of compliance to pharmacopeial standards will fail to also control unwanted elemental impurities. As long as these requirements are met, water can be used without testing for elemental impurities. For pharmaceuticals, the rationale for the acceptability of USP Purified Water is presented in a Pharmacopeial Forum Stimuli for Revision article in PF39(1) – Elemental Impurities in Pharmaceutical Waters, p.434.

    2. Stagnation & Contamination

      1. Water used in the process should not be allowed to sit for long periods of time, especially uncovered.
      2. Water should be checked for purity via pH testing, conductivity testing, and microbial contamination.

  9. Production

    1. Product uniformity

      1. Growth in uniformity of production is associated with an increase in the quality of the products, reduced number of accidents at work, and improved efficiency of the production process.

    2. Approval

      1. Approval of received and produced items is crucial to all Quality Systems.
      2. Quality Approval Process for product and production process helps to provide clear evidence of a structured quality plan for product and process, as required under numerous standards.

    3. Lot tracking

      1. Lot tracking is used for a variety of things, including to trace products through the manufacturing process, shipping, and customer inquiries. Lot numbers can also be used when a recall is necessary, a product needs to be quarantined, or old products are brought out from long-term storage.

Conclusion

Quality is critical to producing consistent products, satisfying customers, and retaining purchasers. Quality is important for customer satisfaction that ultimately results in customer loyalty. Long-term Quality Systems often produce more revenue and profitability. Companies can build a reputation for quality by obtaining accreditation with a recognized quality standard, such as GMP or ISO9001.