Non-sterile Manufacturing GMP Training for Liquids, Creams and Ointments

Opens with the children's cough syrups contaminated with diethylene and ethylene glycol between October 2022 and January 2023, which the WHO linked to more than 300 deaths, and FDA's account of untested glycerin and propylene glycol. Then the DermaRite recall of creams, lotions and soaps in 2025. Explains why these products are at risk: water to grow in, large tanks and many hand-offs. Introduces JKL Pharma's liquids and semisolids block in Mumbai, and outlines the ten modules, practice questions and final exam. You meet the other sites in the course, such as a syrup maker in London and an ointment maker in Frankfurt. The module closes with a recap of the two cases, the three reasons these products are at risk, and how the course works.

What you will be able to do

• Explain why water-based products are open to microbial growth
• Recognise how an untested ingredient can reach thousands of patients
• Ask whether every container of a high-risk ingredient is tested

Why it matters

One wrong ingredient in a large tank can reach thousands of patients in days; knowing the risk is where control begins.

Practice: Practice: Welcome: why non-sterile products need special care · 3 questions

Starts with FDA's review of adverse event reports from 2014 to 2017, with 197 reports linked to contamination and more than 50 recalls for objectionable organisms. Sorts the risks into microbial, and chemical and other contamination, as Annex 9 names them, and explains when an organism is objectionable. Applies five factors to JKL Pharma's suspension PCM120 and cream CLO1, then shows a syrup maker in London that held a tank overnight without a studied hold limit, and the rules behind hold times. You see the written risk summary JKL's quality team wrote for both products, and the rule to prevent first and preserve second. A recap closes the module: know the risk, product by product.

What you will be able to do

• Tell microbial risks from chemical and other contamination
• Explain when an organism counts as objectionable for a product
• Assess a product on the five risk factors

Why it matters

Every control on a non-sterile line needs a reason; a written risk summary per product tells you where to focus.

Practice: Practice: The risks and the rules · 3 questions

Begins at an ointment maker in Frankfurt, where microbial counts crept up until an engineer found a branch pipe where product never drained. Covers Annex 9's recommendation of closed systems for processing and transfer, and filtered air where product must be open. Then equipment designed to be readily cleaned, with no dead legs, steel rather than glass, and rooms with no fibre-shedding materials and a one-way flow. Applies this at JKL Pharma, including the design check on its suspension line. You see what the design check records and how good habits on the floor support the design. The module ends with a recap: design out the places where contamination can hide.

What you will be able to do

• Explain why closed systems protect product during processing
• Recognise dead legs and other places where liquid can sit
• Check a line's design against hygienic design rules

Why it matters

A single hidden pipe can seed every batch that flows through it; designing it out stops contamination at the source.

Practice: Practice: Premises and equipment · 3 questions

Opens at a cough mixture maker in Sydney, where a batch was made with water from a loop restarted after a ten-day shutdown and later rejected. Covers the three parts of Annex 9 point 4: specifying and monitoring water quality, maintaining systems against microbial growth, and validated flushing after chemical sanitisation. Explains biofilm and Purified Water as the minimum for oral and cutaneous products. Walks through JKL Pharma's purified water system, its monitoring plan and its sanitisation and flush record. You see the water system from city water to the mixing vessel, alert and action limits at every point of use, and the restart steps before the first batch. A recap closes the module: treat water as your most important ingredient.

What you will be able to do

• Specify the water quality needed for oral and cutaneous products
• Monitor water at every point of use against alert and action limits
• Release water only after a validated flush and residue test

Why it matters

In a suspension most of every batch is water, so the water system is a production line in its own right.

Practice: Practice: Water: the main ingredient · 3 questions

Returns to the syrup cases, where Indonesian authorities found toxic glycols in a propylene glycol excipient in October 2022, and FDA's May 2023 guidance on trusted certificates and unknown chains of custody. Covers Annex 9 point 5 on checking bulk tanker deliveries before storage, identity of every container, and testing high-risk excipients for diethylene and ethylene glycol against the 0.10% limit. Applies this to sorbitol and glycerin in JKL Pharma's PCM120, its supplier chain and microbial specifications. You see how JKL records the identity test on every container and names the original manufacturer of each lot. The module closes with a recap: trust is built on testing, not on paper.

What you will be able to do

• Check a bulk tanker delivery before it enters a storage tank
• Test every container of a high-risk excipient for toxic glycols
• Trace a material back to its original manufacturer

Why it matters

A trusted drum caused the syrup deaths; testing it yourself and knowing who made it stops a bad lot at the door.

Practice: Practice: Starting materials and high-risk excipients · 3 questions

Opens at a generic syrup maker in Dubai, where an antacid suspension settled as the tank emptied and the last bottles ran low in assay. Walks through how JKL Pharma makes a 1,000 litre batch of PCM120, from checked weights to homogenising and sampling. Covers in-process tests, transfer routes checked by two people, a sampling plan built on point 8, hold-time limits and the most common mistake in filling suspensions. You see JKL's transfer check, its sampling plan with samples from the end of filling, and its hold-time table for PCM120. The module ends with a recap of mixing, transfer and holding: the last bottle must match the first.

What you will be able to do

• Mix to set times, speeds and temperatures, and prove it by testing
• Check a transfer route with a second person before pumping
• Keep a suspension homogeneous to the end of filling

Why it matters

Release tests can look fine while the last bottles are short of active substance; proving homogeneity protects every patient.

Practice: Practice: Making liquids: mixing, transfer and holding · 3 questions

Starts at a cream contract manufacturer in Hong Kong, where condensation from an opened lid dripped into cooling cream and caused mould. Explains emulsions and the three things that decide the result: temperature and cooling rate, shear and speed, and air removed under vacuum. Walks through JKL Pharma's clotrimazole cream CLO1, its critical settings and bulk checks, closed transfer as Annex 9 point 1 recommends, tube tests at start, after stops and at the end, and holding the bulk within studied limits. You see JKL's batch record with each critical setting and its validated range, and its filling record for CLO1. The module closes with a recap: a good cream is made by settings, not by feel.

What you will be able to do

• Explain the critical settings in making an emulsion
• Check tubes for fill weight and assay at start, after stops and at the end
• Treat any change to a validated setting as a recorded deviation

Why it matters

Small changes in heat or speed can spoil a cream; working to validated settings, not feel, keeps every batch right.

Practice: Practice: Making creams and ointments · 3 questions

Begins with the May 2016 case where the CDC told FDA of severe illness in patients in 13 hospitals, linked to a contaminated liquid stool softener. Explains why Burkholderia cepacia complex, at least 17 related species, can feed on preservatives and grow on the shelf, and its likely sources. Follows JKL Pharma's cleaning cycle and record for the CLO1 cream mixer, dirty and clean hold times, drying and weekly swabs, then shows the controls working together at an oral liquids site in Toronto. You see JKL's cleaning record for its cream mixer and how any B C C finding triggers an investigation. The module ends with a recap: keep organisms out, because some cannot be stopped later.

What you will be able to do

• Explain why some organisms can grow despite a preservative
• Clean and dry equipment within dirty and clean hold times
• Check that tests count and identify objectionable organisms

Why it matters

A batch can meet its limit at release and still harm a patient later; keeping organisms out from the start is the only answer.

Practice: Practice: Microbial control and cleaning · 3 questions

Opens at a gel maker in Tokyo that shipped a batch before its microbial test ended and then had to recall it. Covers 21 CFR 211.165 on testing each batch before release, and Chapter 6 of the EU GMP guide with the marketing authorisation. Applies this to JKL Pharma's tests for PCM120, five checks on its packing line, stability from the top and bottom of the bottle, and its release checklist. Explains review of every record and the Qualified Person's role at JKL's EU importer in Dublin. You see JKL's release checklist for PCM120, completed by quality assurance, and the checks that show packing lines run without mix-ups. A recap closes the module: no result, no release.

What you will be able to do

• Check that every result is in and reviewed before release
• Explain how the container and stability support the expiry date
• Describe who makes the release decision in the US and the EU

Why it matters

Shipping before a result is in can cost far more than a few days' wait; no result, no release.

Practice: Practice: Testing, packaging and release · 3 questions

Takes one JKL Pharma batch through six stages: materials, water, making, filling, cleaning and the quality decision. Opens the evidence at each step, from glycol tests against the 0.10% limit and named manufacturers to water results, mixing records and checked transfers. Looks at how the team handled a 40 minute capper stop as a deviation, then covers what inspectors focus on, a readiness checklist for your own site and how the final exam works. Ends with the course in three words: prevent, control, prove. You see the evidence an inspector would ask for at each stage, including the test record for every drum and the water results for the period. The course closes with the final exam, where one retake is included.

What you will be able to do

• Trace one batch's evidence through all six stages
• Handle a filling stop through the restart procedure and a deviation
• Use a readiness checklist on your own site

Why it matters

If an inspector picks one batch, you should be able to show it was made well, record by record.

Practice: Practice: Putting it together: one batch, start to end · 3 questions