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We want to make GMP knowledge easily accessible to all and empower everyone to share their expertise with each other. That way we can keep producing safe and compliant medicine.
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Is Airlocks required for MLT and culture handling room?.
It is Completely depends on the design . There is no specific requirement to have a MAL for Specific Rooms . The main aim to prevent the Contamination/ Cross Contamination. In the culture handling room ( GPT test room ) should have a segregated AHU to prevent Cross Contamination.
It is Completely depends on the design . There is no specific requirement to have a MAL for Specific Rooms . The main aim to prevent the Contamination/ Cross Contamination.
In the culture handling room ( GPT test room ) should have a segregated AHU to prevent Cross Contamination.
See lessReturns Vs Recalls
Dear Nadia, a recall is an action which the manufacturer of the pharmaceutical product initiates, mostly because of a quality issue. In this case, one or more batches needed to be sent back. The authorities need to be informed as well. A product return is an action done by a customer. This can be quRead more
Dear Nadia,
a recall is an action which the manufacturer of the pharmaceutical product initiates, mostly because of a quality issue. In this case, one or more batches needed to be sent back. The authorities need to be informed as well.
A product return is an action done by a customer. This can be quality-related or not. If it is quality-related, the manufacturer should conduct an investigation and if needed initiate a recall.
See lessHow many containers of each component from each shipment must a firm sample and test to comply with the CGMP requirements for identity testing? Do the CGMPs permit the identity test on a pooled, or composite, sample of multiple containers?
The CGMPs address the issue of sample compositing directly but only in the context of individual container sampling. Section 211.84(c)(4) explicitly prohibits compositing samples taken from the top, middle, and bottom of a single container when such stratified sampling is considered necessary (as miRead more
The CGMPs address the issue of sample compositing directly but only in the context of individual container sampling. Section 211.84(c)(4) explicitly prohibits compositing samples taken from the top, middle, and bottom of a single container when such stratified sampling is considered necessary (as might be the case when moisture content needs to be controlled, particularly when only a portion of a container may be used in a drug product batch). The preamble for § 211.84(c)(4) explains further that there “is no general prohibition… on compositing samples [from single containers] where such compositing would not mask subdivisions of the sample that do not meet specifications” (see 1978 preambleExternal Link Disclaimer, paragraph 231).
Testing individual samples from multiple containers provide a high level of assurance and are consistent with CGMP. Testing a composite model for identity could satisfy the CGMP regulations (§§ 211.84 and 211.160) but only if a manufacturer demonstrates either that the detection of a single non-conforming container is not masked by compositing or that an additional test(s) routinely performed on the composite sample ensures that all containers sampled contain the same material. Thus, a purity assay on a composite sample prepared by mixing equal aliquots from each container may be acceptable, provided such a test is sufficiently sensitive to reveal the presence of a single non-conforming container.
References:
The preamble to the Current Good Manufacturing Practice in Manufacture, Processing, Packing, or Holding regulations (43 FR 45014, Sept 29, 1978)
21 CFR 211.82: Receipt and storage of untested components, drug product containers, and closures
21 CFR 211.84: Testing and approval or rejection of components, drug product containers, and closures
21 CFR 211.160: General requirements (Laboratory Controls)
FDA Guidance for Industry, 2000, ICH Q6A Specifications: Test Procedures and Acceptance Criteria for New Drug Substances and New Drug Products: Chemical Substances [Text or PDF]
FDA Guidance for Industry, 1999, ICH Q6B Specifications: Test Procedures and Acceptance Criteria for Biotechnological/Biological Products [PDF]
See lessIs it acceptable to simply segregate products of a common therapeutic classification
Manufacturers cannot just segregate everyday products from other product types to deal with the risk to patient and animal safety. Although this may prevent contamination of other product classes, it does not address cross-contamination within product classes. This should include implementing appropRead more
Manufacturers cannot just segregate everyday products from other product types to deal with the risk to patient and animal safety. Although this may prevent contamination of other product classes, it does not address cross-contamination within product classes.
This should include implementing appropriate organisational and technical control measures to prevent contamination between such products within product-specific HBELs.
See lessWhat are the Specs and Requirements for conducting visual inspection as per Q&A 7?
When applying visual inspection to determine the cleanliness of equipment, manufacturers should establish the threshold at which the product is readily visible as a residue. This should also consider the ability to visually inspect the equipment, for example, under the lighting conditions and distanRead more
When applying visual inspection to determine the cleanliness of equipment, manufacturers should establish the threshold at which the product is readily visible as a residue.
This should also consider the ability to visually inspect the equipment, for example, under the lighting conditions and distances observed in the field. Visual inspection should include all product contact surfaces where contamination may be held, including those that require dismantling of equipment to gain access for inspection and by use of tools (for example, mirror, light source, boroscope) to access areas not otherwise visible.
Non-product contact surfaces that may retain products that could be dislodged or transferred into future batches should be included in the visual inspection. Written instructions specifying all areas requiring visual inspection should be in place, and records should confirm that all inspections are completed. Operators performing visual inspection need specific training in the process, including periodic eyesight testing. Their competency should be proven through a practical assessment.
See lessIs analytical testing required at product changeover, on equipment in shared facilities, following completion of cleaning validation?
Analytical testing is expected at each changeover unless justified via a robust, documented Quality Risk Management (QRM) process. The QRM process should consider, at a minimum, each of the following: - the repeatability of the cleaning process (manual cleaning is generally less repeatable than autoRead more
Analytical testing is expected at each changeover unless justified via a robust, documented Quality Risk Management (QRM) process.
The QRM process should consider, at a minimum, each of the following:
– the repeatability of the cleaning process (manual cleaning is generally less repeatable than automated cleaning);
– the hazard posed by the product;
– whether visual inspection can be relied upon to determine the cleanliness of the equipment at the residue limit justified by the HBEL.
See lessWhat responsibility do contract givers have to contract manufacturers in relation to data to support a HBEL assessment?
Contract givers should either provide a full HBEL assessment to contract manufacturers or provide the data to allow the contract manufacturer to conduct the HBEL assessment. In either case, the HBEL assessment, including data references and relevant experts, should be available on request during theRead more
Contract givers should either provide a full HBEL assessment to contract manufacturers or provide the data to allow the contract manufacturer to conduct the HBEL assessment.
In either case, the HBEL assessment, including data references and relevant experts, should be available on request during the manufacturer’s inspection.
Although the EMA guideline (EMA/CHMP/CVMP/SWP/169430/2012) may be used to justify cleaning limits (as per Introduction paragraph 3), it is not intended to be used to set cleaning limits at the level of the calculated HBEL.
For existing products, the manufacturer’s historically used cleaning limits should be retained. They can be considered alert limits provided that when taking cleaning process capability into account, they provide sufficient assurance that excursions above the HBEL will be prevented. A similar process should be adopted when establishing cleaning alert levels for products introduced into a facility for the first time.
Results above the alert cleaning limit should trigger an investigation and, where appropriate, corrective action to bring the cleaning process performance within the alert cleaning limits. Repeated excursions above the alert cleaning limit will not be considered acceptable, where these indicate that the cleaning method is not in control. Recognised appropriate statistical methods may be used to determine whether the cleaning process is in control or not.
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