Deficiency examples

MHRA

Data integrity assessments were focused on system compliance and failed to consider the impact of business processes on the integrity of data, for example manual transfer of data between electronic systems.

MHRA

The investigation relating to a data integrity failure, whereby fictitious utility monitoring data was recorded, lacked sufficient detail to demonstrate whether willful intent was suspected.

MHRA

Setting within HPLC software not fully enabled e.g. audit trail

MHRA

There were no settle plates located close to the point of fill to provide adequate assurance during exposure periods that EU GMP Annex 1 grade A limits were being met

MHRA

The continuous particle monitoring sample points were located too high in relation to the relevant work zones to provide meaningful data to demonstrate that EU GMP Annex 1 requirements were being met

MHRA

The wipes used for sanitisation did not appear to be wetted sufficiently as only the area in the centre appeared to be wet rather than the whole area to ensure effective surface coverage.

PMDA

The inspected site did not have a procedure for informing marketing authorization holder when a change having impact to the product quality is implemented.

MHRA

Changes were implemented outside of the company’s Change Control procedure.

MHRA

There is no definition of which moderate level change controls would require a risk assessment and regulatory affairs review and which would not.

MHRA

Access to files and the system clock on the hard drive were available to all users.

MHRA

The lock screen used a shared password. If a user had logged into the software behind the lock screen and another user opened the computer, they could perform actions under the initial user’s login.

MHRA

Users had more authorisation on the chromatography data system than was permitted according to the SOP.

MHRA

Deviation reports did not contain sufficient information to describe the investigations conducted or demonstrate the evidence that supported the proposed root cause.

MHRA

There was no requirement to ensure that process, procedural or systems based errors had not been overlooked prior to identifying ‘Personnel Error’ as a root cause.

MHRA

At least 8 overdue CAPA (ranging from 59 days to 242 days overdue) were observed to have been closed the day before the inspection.

MHRA

There were no log books in place for each compounding workstation to ensure traceability of operations.

PMDA

However, the inspection found that a wide range of records had been discarded, including X records of QC, X records of X of X, and usage records of X and X.

MHRA

Non-contemporaneous recording was noted during placebo manufacture as the date completed for the process step on the batch production record had already been entered before that process step had actually been completed.

PMDA

The procedure for handling OOS events does not necessarily require root cause analysis nor implementation of CAPA, even no laboratory error or sampling error was identified in the initial phase investigation.

PMDA

Reconciliation and related records of working standards used for product release test, including use date, used amount are not recorded.

MHRA

There was no justification for the twelve month expiry assigned to reagents.

MHRA

Permitted limits for carryover of organic molecules have not been set or adequately risk assessed

MHRA

Swab samples have not been taken, in particular no swabs have been taken from difficult to clean areas where other methods or determining residues may not be effective

MHRA

No cleaning validation had been performed on the dispensing isolator.

MHRA

A jug of cleaning liquid with a used cloth was found sitting on the capsule polishing unit that had been signed off as clean.

MHRA

The automated tablet counter and tablet counting trays, which were used for multiple products, had not been considered as part of the cross contamination risk assessment

MHRA

Sanitisation contact times were not being monitored and the five minutes contact time for the sporicide was not as defined by the sanitising agent manufacturer or validated by the Company.

MHRA

The clean room was only monitored after cleaning. There was no periodic monitoring before cleaning to monitor for potential microbial changes or for the continuing effectiveness of cleaning

MHRA

Not all phases of production were subject to microbial monitoring, e.g. activities with no cellular product present such as preparation of equipment, which has a similar potential for contamination of product

MHRA

The management review process was deficient, for example, the meeting minutes stated that all environmental monitoring results were satisfactory; despite there being an obvious adverse trend increase in clean room environmental monitoring results.

MHRA

Procedures did not describe the basis for accepting an audit report prepared by a third party.

MHRA

The approved supplier list does not include the address of the manufacturer. The site is therefore unable to confirm that the material is received from both the correct supplier and manufacturer.

MHRA

Only the top layer of large dry powder chemical drums was being sampled so this material was not representative of the bulk material.

MHRA

Inadequate investigation was performed on site. For example, not reviewing manufacturing and other data available and also not considering the wider implications of the complaint on other batches.

MHRA

The recall procedure did not define maximum timelines for key steps to ensure the recall process was completed in a timely fashion.

MHRA

The mock recall challenge was not completed in a timely manner and no final formal assessment report was generated.

MHRA

Personnel had no documented training in the procedures or systems

MHRA

Although comprehension questions were asked at the end of each module, there was no clearly defined pass mark therefore it could not be confirmed that the personnel understood the training

MHRA

There was no system for confirming that all personnel that required training had been trained.

MHRA

There was no confirmation that the ongoing stability studies showed no adverse trends and would be expected to remain within specification for the proposed shelf life.

MHRA

There had been numerous stability failures (including pre- shelf life expiry) identified but these had not been formally assessed by the QPs or the impact on continued certification considered.

MHRA

The contract manufacturer did not notify the stability failures to the Marketing Authorisation Holders.

PMDA

Multiple scratches resulting from abrasion were found on the internal part of the mill.

MHRA

There was no demarcation between clean and dirty sides of the change room entering the formulation area.

MHRA

The door seal on the coating machine was not intact and had sections missing.

MHRA

There was no formal Management review process.

PMDA

Though the executive management mention lack of human resources in the report of management review, and continuously took actions to retain personnel, those actions did not result in resolution of lack of resources.

MHRA

The management team was not seen to be reacting effectively to poor key performance indicators.

MHRA

Batch processing parameter ranges were not always supported by process validation data, for example the coating flow rate and the granulation chopper speed.

MHRA

There is no clear indication in the process validation protocol that validation batches are predefined as potentially releasable for commercial sale.

MHRA

There was no routine re-validation of manufacturing processes.