Industries · Sterile products

Sterile products step by step.

Aseptic preparation and terminal sterilisation. Below: the path of one batch as the rules describe it, what MALUTI records at each step, and every record type these documents ask for — built or not yet.

The path of a batch

Sterile medicinal products · EU GMP Annex 1 · 23 steps

Your certificate, line by line →

Terminally sterilised

The product is sterilised inside its final container, and the annex says plainly this assures sterility better than filtering and filling aseptically. What it asks for instead is the cycle: a validated load pattern, a record per run under its own identifier, and a release that cannot happen over a cycle nobody approved.

Aseptically prepared

Nothing is sterilised at the end, so every step has to hold on its own. Six more requirements than the terminal route: interventions listed and recorded by time and person, seven declared maximum times, the filter tested before and after use, the people monitored, and the whole process simulated twice a year on every line and every shift.

Before anything is made

The site has a contamination control strategy
1 of 2 built

A contamination control strategy implemented across the facility, defining every critical control point, reviewed and updated, with changes assessed against it before and after they are made.

Annex 1 §2.3, §2.6
The clean room is qualified, and requalified on time
1 of 2 built

Qualification covering filter integrity, airflow volume and velocity, pressure difference, airflow direction, microbial contamination, temperature, humidity and recovery; requalified within six months for grade A and B, twelve for C and D.

Annex 1 §4.25, §4.32
Nobody enters unsupervised without passing the gowning assessment
2 of 3 built

Assessment and reassessment at least annually, visual and microbial, with unsupervised access to grade A and B restricted to those who passed it and took part in a successful simulation.

Annex 1 §7.4
The water is sampled on a plan, every day it is used
Not built yet

Ongoing chemical and microbial monitoring covering all outlets and points of use at a stated interval, with at least one representative sample on every day water is used in manufacturing.

Annex 1 §6.13
Rooms are cleaned and disinfected to a written programme
1 of 2 built

A written programme with more than one disinfecting agent and the periodic use of a sporicidal one; the disinfection process validated, including the in-use expiry of prepared solutions.

Annex 1 §4.33, §4.34

Making and filling

Filling happens in a graded environment
1 of 2 built

Filling of products for terminal sterilisation carried out in at least a grade C environment.

Annex 1 §8.3
The bulk is filtered, and it does not wait indefinitely
1 of 2 built

A filtration step with a microorganism retaining filter before filling, and a maximum permissible time between preparation and filling.

Annex 1 §8.5
Every intervention into the line is on the list and in the record
1 of 2 built

An authorised list of allowed and qualified interventions; each intervention and line stoppage recorded in the batch record with its time, duration and the operators involved. A non-qualified one needs the quality unit and counts at batch disposition.

Annex 1 §8.16, §8.17
Each stage is held inside a declared maximum time
Not built yet

A validated maximum for each: cleaning to sterilisation, sterilised items before use, a decontaminated environment before use, preparation through to the end of filling, sterilised product before filling, the aseptic processing time and the filling time.

Annex 1 §8.18
The sterilising filter is tested before use and after use
Not built yet

Integrity of the sterilised filter assembly verified before use, and a non-destructive integrity test after use before the filter leaves its housing. The test process validated and its results tied to the retention the filter was validated for.

Annex 1 §8.87
Bioburden is taken from the bulk before the final filter
2 of 3 built

A bioburden assay on each batch, aseptically filled and terminally sterilised alike, sampled immediately before the final sterilising filter or the sterilisation process, against a defined limit and considered at batch review.

Annex 1 §8.93, §10.3
What has been sterilised is told apart from what has not
Not built yet

A clear means of differentiating products, equipment and components that have been through the sterilisation process from those that have not, with carriers labelled or electronically tracked by product, batch and that state.

Annex 1 §8.44

Sterilising

The product is sterilised in its final container where it can be
1 of 2 built

Terminal sterilisation by a validated and controlled process wherever possible, because it assures sterility better than filtration and aseptic processing; where it is not possible, a recorded consideration of post-aseptic heat treatment.

Annex 1 §8.34
Every sterilisation process and every load pattern is validated
1 of 2 built

Validation by physical measurement and, where appropriate, biological indicators; validated loading patterns with maximum and minimum loads; heat cycles revalidated at least annually for worst-case patterns.

Annex 1 §8.36, §8.38, §8.39
Every run leaves a record under its own identifier
1 of 2 built

Sterilisation records available for each run, each cycle carrying a unique identifier, their conformity reviewed and approved as part of batch certification and release.

Annex 1 §8.45

Watching while it runs

The room is watched while the work is happening
1 of 2 built

A documented environmental monitoring programme with locations, frequency, methods and incubation from a risk assessment; alert levels and action limits set for viable and total particles, and periodically reviewed against trend data.

Annex 1 §9.4, §9.9
An exceeded limit names the batches it touched
2 of 3 built

A root cause investigation, an assessment of the potential impact on product including batches made between the monitoring and the reporting, and the corrective and preventive actions that follow.

Annex 1 §9.13
The people in the room are monitored too
Not built yet

Microbial monitoring of personnel in grade A and grade B, with more weight on gown monitoring where the operation is manual, justified in the contamination control strategy.

Annex 1 §9.26
The aseptic process is simulated on a schedule
Not built yet

Three consecutive runs at initial validation, then twice a year for each aseptic process, each filling line and each shift, every operator in at least one a year; each run documented with a reconciliation of units filled, incubated and not incubated.

Annex 1 §9.38, §9.47
A failed simulation reaches back over what the line already made
1 of 2 built

Investigation of the root cause, a review of every record of aseptic production since the last successful simulation, product made on that line quarantined until the failure is resolved, and production resumed only after successful revalidation.

Annex 1 §9.46

Before it leaves

Every filled container is inspected, and the defects are trended
1 of 2 built

Individual inspection of all filled containers of parenteral products against a maintained defect library; results recorded, defect types and numbers trended, and a batch with unusual levels investigated against the routine numbers of its line.

Annex 1 §8.30, §8.33
Sterility is tested on the riskiest part of the batch
Built in MALUTI

Samples representative of the whole batch and taken in particular from the parts most at risk: for aseptic filling the beginning and the end of the batch, for heat sterilisation the slowest part of the load to heat.

Annex 1 §10.6
Nothing is certified over an open non-conformity
2 of 3 built

Sterility test failures, environmental excursions and deviations investigated before certification, with the reason for including or excluding a batch recorded; and the environmental data for the time of manufacture reviewed as part of release.

Annex 1 §3.2, §10.10

What the rules ask, and what is built.

EU GMP Part I · EU GMP Annex 1, and the path of a batch above. 52 of 112 record types kept in MALUTI · 58 not built yet · 2 outside the software.

A record type in our catalogue is one thing a clause asks a site to record. Each is counted once, even when two documents or a step of the path ask for it. “Kept in MALUTI” covers what MALUTI does itself and the record it keeps of work your site does. The count shows what we have mapped, not a share of the regulation.

Not built yet (58)

Keep a visitor policy with classes of person EU GMP ch. 2 §2.13
Use only starting materials that Quality Control has released EU GMP ch. 5 §5.34
Clear the work area and equipment before a processing operation starts EU GMP ch. 5 §5.40
Record who took material out of store for a run EU GMP ch. 5 §5.37
Derive the exposure limits behind a shared line EU GMP ch. 5 §5.20
Hold the periodic management review of the quality system EU GMP ch. 1 §1.6
Take the daily statement that bars a person from the clean room, and act on it EU GMP Annex 1 §7.7, §7.8
Qualify a person for aseptic gowning, and reassess at least annually EU GMP Annex 1 §7.4
Disqualify a person from the clean room, and let them back only through requalification EU GMP Annex 1 §7.6
Qualify each operator who inspects filled containers, at least annually and with an eyesight check EU GMP Annex 1 §8.31
Declare how many people a clean room may hold at once, and keep to that number EU GMP Annex 1 §7.2
Let an unqualified person into grade A or B only as a recorded exception, under a named supervisor EU GMP Annex 1 §7.5
Hold the written description of how a machine is built, and keep it current EU GMP Annex 1 §5.1
Acknowledge every process and equipment alarm, and trend them; critical ones are looked at at once EU GMP Annex 1 §5.2
Approve a machine back into use after maintenance, and assess what unplanned work did to sterility EU GMP Annex 1 §5.6, §5.7
Qualify a clean room and requalify it before its interval runs out EU GMP Annex 1 §4.25, §4.32
Disinfect clean rooms to a written programme, and validate it EU GMP Annex 1 §4.33, §4.34
Run the environmental monitoring programme, with an alert level below the action limit EU GMP Annex 1 §9.4, §9.9
Investigate an exceeded action limit and name the batches it touched EU GMP Annex 1 §9.13
Sample the water system on a plan, and investigate its excursions EU GMP Annex 1 §6.13, §6.14
Trend the environmental results by the patterns the annex names, including a change in the flora itself EU GMP Annex 1 §9.11
Monitor grade A without a break for the whole of critical processing, and raise an alarm at the alert level EU GMP Annex 1 §9.16, §9.17, §9.24
Sample gloves and gown after every critical intervention and on each exit from grade B EU GMP Annex 1 §9.25, §9.26
Identify what grew in grade A or B down to the species, and judge what it means for each batch implicated EU GMP Annex 1 §9.31
Hold the approved list of what may be taken into grade A and B, and record every exception to it EU GMP Annex 1 §4.12
Hold the airflow visualisation studies, at rest and in operation, with the recordings they produced EU GMP Annex 1 §4.15
Record the air pressure differences between rooms, and record what was decided when the warning fired EU GMP Annex 1 §4.16
Run the barrier bio-decontamination cycle inside its validated parameters, and record each run EU GMP Annex 1 §4.22
Hold the clean-up period the room was qualified with, and do not call the room clean before it has passed EU GMP Annex 1 §4.29
Keep the installation record of each utility system for its whole life: drawings, materials, specification EU GMP Annex 1 §6.5
Trend the critical parameters of every high-risk utility, not only its excursions EU GMP Annex 1 §6.4
Sanitise the water system on its schedule, and hold every batch made on that water until its results are approved EU GMP Annex 1 §6.12
Hold the quality of every process gas, and monitor it microbially at the point of use EU GMP Annex 1 §6.18, §6.19
Keep the contamination control strategy, and review it EU GMP Annex 1 §2.3, §2.6
Hold the authorised list of interventions, and record each one in the batch record with its time, duration and operator EU GMP Annex 1 §8.16, §8.17
Hold each stage of aseptic processing inside its declared maximum time EU GMP Annex 1 §8.18
Tell what has been through the steriliser from what has not EU GMP Annex 1 §8.44
Record every sterilisation run under its own identifier, and approve it at release EU GMP Annex 1 §8.45
Validate the sterilisation loads, and revalidate them on schedule EU GMP Annex 1 §8.36, §8.38, §8.39
Test the sterilising filter before use and after use, and keep both results with the batch EU GMP Annex 1 §8.87
Take bioburden from the bulk immediately before the final filter, against a declared limit EU GMP Annex 1 §8.93, §10.3
Inspect every filled container, and trend the defects found EU GMP Annex 1 §8.30, §8.33
Run the aseptic process simulation on its schedule, and document it with a reconciliation of units EU GMP Annex 1 §9.38, §9.47
On a failed simulation, quarantine what the line made since the last good one EU GMP Annex 1 §9.46
Have aseptic operations watched by someone expert in them, on a regular basis, and act on what is seen EU GMP Annex 1 §8.19
Test container closure integrity — every fused container, a justified sample of the others EU GMP Annex 1 §8.22, §8.23, §8.24
Challenge the automated inspection machine with known defects before start-up and during the batch EU GMP Annex 1 §8.32
Detect a sterilisation cycle that left its validated parameters, and investigate it EU GMP Annex 1 §8.35, §8.41
Run a positive control for every cycle that uses biological indicators, and verify each new indicator batch before use EU GMP Annex 1 §8.42, §8.43
Inspect each item leaving the steriliser for dryness, damage and packaging integrity, and investigate what fails EU GMP Annex 1 §8.56, §8.57
Put the filtration parameters into the batch record, and investigate a run that differs from them EU GMP Annex 1 §8.86
Test critical gas and vent filters after use, record the others at intervals, and hold their maximum duration of use EU GMP Annex 1 §8.88, §8.89
Discard a sterilising filter after one batch, or hold a validated campaign duration and refuse to pass it EU GMP Annex 1 §8.94, §8.95
Sterilise the lyophiliser on its justified frequency, and check its leak rate at the start of every cycle EU GMP Annex 1 §8.122, §8.124
Record the critical parameters of each form-fill-seal or blow-fill-seal run, and investigate rejected units EU GMP Annex 1 §8.102, §8.103, §8.116, §8.117
Incubate every integral simulation unit, justify each one not incubated, and have them read by a qualified person against a positive control EU GMP Annex 1 §9.41, §9.43, §9.44, §9.45
Justify in writing which batches an investigation covers, and close it before the batch is certified EU GMP Annex 1 §3.2
Review the environmental data of the time of manufacture, and its trend, as part of releasing the batch EU GMP Annex 1 §10.10

Built in MALUTI (49)ShowHide

Record what a person is qualified by EU GMP ch. 2 §2.1
Keep the record of a consultant: name, address and service EU GMP ch. 2 §2.23
File fitness for work EU GMP ch. 2 §2.16
Record training and its expiry EU GMP ch. 2 §2.10–2.12
Assess periodically whether training actually worked EU GMP ch. 2 §2.11
Keep training programmes approved by the head of Production or of Quality Control EU GMP ch. 2 §2.11
Grant access to rooms EU GMP ch. 3 §3.5
Keep an organisation chart showing who answers to whom EU GMP ch. 2 §2.2
Write down the duties and the authority of a responsible position EU GMP ch. 2 §2.3
Declare what each room must hold, and watch it EU GMP ch. 3 §3.19
Register equipment and its qualification EU GMP ch. 3 §3.34, §3.41
Keep the use and cleaning log of each machine EU GMP ch. 4 §4.31
Examine each container: labels, damage, broken seals EU GMP ch. 5 §5.30
Run an identity test on every batch received EU GMP ch. 5 §5.35
Hold incoming material in quarantine until released EU GMP ch. 5 §5.5
Hold the approved manufacturing formula, with its versions and its effective date EU GMP ch. 4 §4.17, §4.3
Define a process as data, with its limits EU GMP ch. 4 §4.18
Start and run a process EU GMP ch. 4 §4.20
Investigate a significant deviation from expected yield EU GMP ch. 5 §5.44
Run an on-going stability programme EU GMP ch. 6 §6.27–6.31
Trend results and investigate what falls outside EU GMP ch. 6 §6.9, 6.35
Raise and close deviations EU GMP ch. 5 §5.15
Run CAPA through action and verification EU GMP ch. 1 §1.4(xiv)
Raise an incident and find the batches around it EU GMP ch. 8
Record a complaint from outside: who complained, what was answered, and what happened to the batch EU GMP ch. 8 §8.5–8.14
Run self-inspection to a programme EU GMP ch. 9
Approve and supersede procedures EU GMP ch. 4
Register counterparties and score suppliers EU GMP ch. 7
Compile the annual product quality review EU GMP ch. 1 §1.10
Recall released product EU GMP ch. 8 §8.22–8.30
Control packaging materials and their storage EU GMP ch. 5 §5.46
Clear the line before packing, and record it EU GMP ch. 5 §5.50
Issue, reconcile and destroy labels EU GMP ch. 5 §5.46, §5.61, §5.62
Record a batch that came back: from whom, how much, why, and what was done with it EU GMP ch. 5 §5.70
Assemble a batch dossier EU GMP ch. 4
Test the barrier glove system for leaks at the start and end of each batch, and look at it at every use EU GMP Annex 1 §4.21
Hold each clean room garment as an item: its sterilisation, its hold time, its laundry count and the point it is replaced EU GMP Annex 1 §7.11, §7.15, §7.17
Hold each disinfectant as a batch: sterile for grade A and B, dilutions monitored and given an expiry EU GMP Annex 1 §4.35
Test pure steam on a schedule — condensate to the monograph, plus non-condensable gases, dryness and superheat EU GMP Annex 1 §6.17
Check the sterile barrier of each sterilised item before use, and hold the shelf life its packaging was validated for EU GMP Annex 1 §8.48
Run the steriliser leak test weekly and the air removal test daily, and keep both results EU GMP Annex 1 §8.60, §8.61
Check each single-use system on receipt against its specification and its proof of sterilisation EU GMP Annex 1 §8.134, §8.138
Take a sample to a sampling plan EU GMP Annex 1 §10.6
Test each batch of medium for growth promotion before it is used, and justify any reliance on the supplier EU GMP Annex 1 §10.9
Keep the risk matrix and the validation file ICH Q9 · path step Annex 1 §2.3, §2.6
Qualify equipment through URS, IQ, OQ, PQ EU GMP Annex 15 §3 · path step Annex 1 §4.25, §4.32
Approve a specification, every limit naming its method EU GMP Annex 7 §8 · path step Annex 1 §8.93, §10.3
File a certificate of analysis and let it be judged Lesotho LN40 reg. 20(8) · path step Annex 1 §10.6
Release a batch EU GMP Annex 16 §1.6 · path step Annex 1 §3.2, §10.10

Done by the site, recorded in MALUTI (3)ShowHide

Maintain buildings, floors, lighting, changing rooms EU GMP ch. 3 §3.2, §3.3, §3.31
Control pests in storage, by authorised people only EU GMP ch. 3 §3.4
Hold written contracts for outsourced work EU GMP ch. 7 §7.14–7.17

Outside the software (2)ShowHide

Examine a person medically and read the finding EU GMP ch. 2 §2.16
The examination is a doctor's work and the finding is medical. We hold the outcome in three words, the dates and who recorded them. A field for a diagnosis does not exist anywhere in this system, because a record that only ever grows cannot take a disclosure back.
Run the analysis itself EU GMP ch. 7
The laboratory has its own accreditation, its own methods and its own instruments. We hold the certificate and its hash, the limits it was judged against, the verdict, and the state of that laboratory's licence on the day it signed.

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Sterile products step by step.

The path of a batch

Terminally sterilised

Aseptically prepared

The site has a contamination control strategy

The clean room is qualified, and requalified on time

Nobody enters unsupervised without passing the gowning assessment

The water is sampled on a plan, every day it is used

Rooms are cleaned and disinfected to a written programme

Filling happens in a graded environment

The bulk is filtered, and it does not wait indefinitely

Every intervention into the line is on the list and in the record

Each stage is held inside a declared maximum time

The sterilising filter is tested before use and after use

Bioburden is taken from the bulk before the final filter

What has been sterilised is told apart from what has not

The product is sterilised in its final container where it can be

Every sterilisation process and every load pattern is validated

Every run leaves a record under its own identifier

The room is watched while the work is happening

An exceeded limit names the batches it touched

The people in the room are monitored too

The aseptic process is simulated on a schedule

A failed simulation reaches back over what the line already made

Every filled container is inspected, and the defects are trended

Sterility is tested on the riskiest part of the batch

Nothing is certified over an open non-conformity

What the rules ask, and what is built.

Not built yet (58)

Let’s map MALUTI to your site.