TOPIC 7: Laboratory Controls

Quality Control

• Ensures all necessary and relevant tests are done according to SOPs in GMP labs

• Has the authority to approve or reject any components of the process (eg. in-process materials, drug products, packaging materials, containers and closures)

• Involved in all quality decisions (not just lab work!)

  • Reviews and approves procedures/specifications affecting product quality (efficacy, purity)

• Key QC functions (testing) – All tests MUST comply with predetermined specifications. Any deviation or out-of-specifications (OOS) must be recorded and investigated

  • Routine Sampling & Testing: Raw materials, bulk and final products, packaging, utilities (gases, water) and environmental monitoring (particulate and microbial)

  • In-process Testing: Checks intermediates in process up and downstreams to decide the next step

  • Ad-hoc Testing: For product changeover, validation or sample investigations (eg. cleaning rinse water, surface swab samples etc.)

• QC is IMPORTANT in biopharma production and control as it is a primary way of testing product quality

• The test results guarantees the product quality is acceptable so anything in the testing process that could influence these results is a major concern

QC Laboratory Equipment

• Refers to critical instruments, gauges, and devices used for testing (eg. Measuring instruments, apparatus, gauges and recording devices)

• New equipment must be commissioned and qualified

• Calibrate equipment regularly per a written program to ensure accuracy and precision

• Do not use if it fails to meet specifications

Sampling, Testing and Release

• Procedures must include sampling method, sample size, number of samples, and acceptance criteria

• Samples shall be representative and clearly identified

• Test methods must be established, documented (eg. SOPs or manuals) and validated for:

  • Accuracy – Closeness of measured value to the ‘true’ value

  • Precision – Closeness of ≥ 2 measurements to each other

  • Sensitivity – Depends on method detection limit and response to small differences

  • Specificity – Test method focus on target analyte only

• All batch test results must meet all written specifications (eg. identity, strength, purity) before releasing to the market

  • Certificate of Analysis (COA) will accompany each batch release

• Retesting is only allowed if investigations prove a test procedure error

  • Retesting procedure to be pre-defined

Stability Testing

• A long-term (ie. 3 – 5 years) testing program to study drug characteristics (eg. API content, level of degradation and microorganisms) over time and storage conditions 

• To determine appropriate storage conditions and expiration dates

• Performed on raw materials, APIs, finished products or components

• Testing done on the product must be in its final marketed packaging (eg. bottle, blister)

Stability Test Process

• Before – Plan the attributes to test, sample size, test intervals and acceptance criteria

• During – Place samples in stability chambers with preset temperature and humidity and retrieve them at planned intervals for analysis

• After – Analyze data trends over time and submit to regulatory agencies to justify the shelf life

Reserve Samples

• Identified samples that are retained and represent each batch of API in each shipment

  • Retain at least double the quantity needed for full testing (to determine if API meets specifications)

• Perform annual visual checks for deterioration and investigate where necessary

• Test both before and after reconstitution for freeze-dried biologic products

• Store under labeled conditions and in the product’s marketed container

• Keep for 1 year past the batch's expiration date

Starting Materials

• Each lot must have an appropriately identified status – Quarantined, Approved or Rejected

• To be stored under manufacturer-specified conditions

• Organise for clear batch segregation and follow FIFO or FEFO

  • Minimises waste from expired materials