Manufacturers should ensure that the products are safe, effective and of the quality required for their intended use. Systems should be in place to ensure that pharmaceutical products are produced according to validated processes and to defined procedures.
Manufacturing processes should be shown to be capable of consistently manufacturing pharmaceutical products that are of the required quality and that comply with their specifications.
GMP require that arrangements should be made to ensure that the dispensed raw materials and packaging materials, intermediate products, bulk and finished products are stored under appropriate conditions.
Storage arrangements should not have deleterious effects on starting materials, intermediate products and bulk products prior to final packing.
Maximum acceptable holding periods should therefore be established to ensure that intermediates and bulk product can be held, pending the next processing step, without producing results outside the acceptance criteria for the quality of the material.
Normally, intermediate and bulk products should not be stored beyond the established hold time.
The choice of maximum holding period should be supported by relevant data.
Hold-Time Studies
Hold time studies establish the time limits for holding the materials at different stages of production to ensure that the quality of the product does not produce results outside the acceptance criteria during the hold time.
The design of the study should reflect the holding time at each stage.
Justification of Time-Limit Deviation Should Include:
- How can minor or gross deviation from the specified time limit be justified when the time limit selected is somewhat arbitrary?
- Why would holding a bulk biopharmaceutical drug substance for 24 hours be allowable but 25 hours would not?
- Is repeating a process step a reasonable response to exceeding the time limitation?
Avoidance of Holding In-Process Materials
- Many strategies are being implemented to avoid the holding of in-process material.
- The drivers are controlling risk, lowering manufacturing costs and shortening the manufacturing, time and decreasing in-process intermediate inventories, work-in-progress and prevent potential back orders.
- These strategies include continuous manufacturing, clean- and sterilize-in-place, and continuous sterile filtration and aseptic filling.
Reliability
Reliability is the probability that a product, system, or service will perform its intended function adequately for a specified period of time, or will operate in a defined environment without failure.
Although stochastic parameters may define and affect reliability, multivariate inputs with wide ranges of uncertainty largely invalidate quantitative methods of reliability, especially as applied to pharmaceutical drug products.
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Resource Person: BARBARA PIROLA
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