EU GMP Annex 7 Training: Herbal Medicinal Products from Field to Release

Opens with pyrrolizidine alkaloids, toxic substances made by weeds that grow among the crop, which the European Medicines Agency's herbal committee has worked on for more than ten years, and its daily limit for an adult. You then learn why herbal medicines are different: complex, variable materials that can carry soil, insects, moulds and seeds into the factory, where quality starts with who grew the plant and how it was harvested and dried. You meet JKL Pharma, a tablet maker in Mumbai making SNT1 senna dry extract tablets from leaves grown by contract farmers in southern India, held in the EU by JKL Pharma Europe in Dublin. The module sets out who the course is for, the scope of Annex 7, the ten modules and exam, and ends with a recap.

What you will be able to do

• Explain why herbal materials need different controls from chemicals
• Describe the contamination risk from toxic weeds in the crop
• Identify what EU GMP Annex 7 covers and what it leaves out

Why it matters

Seeing that quality starts in the field prepares you to control herbal risks that a factory test alone cannot catch.

Practice: Practice: Welcome: why herbal medicines are different · 3 questions

Starts with a question often heard: does a herbal medicine registered on long tradition need less GMP? You then learn the two definitions of a medicinal product in Directive 2001/83/EC, by presentation and by function, and the legal definitions of a herbal substance, a herbal preparation and a herbal medicinal product, defined by plant part and botanical name. JKL Pharma's dried senna leaflets and senna dry extract are classified against them. The module explains the two routes to market, a marketing authorisation or a traditional-use registration based on at least 30 years of medicinal use, 15 of them in the EU, and the role of JKL Pharma Europe in Dublin and its Qualified Person. It ends with four signs that a site applies the same GMP to every product, and a recap.

What you will be able to do

• Tell a herbal substance, preparation and medicinal product apart
• Explain the two routes to the EU market for herbal medicines
• Explain why GMP applies in full on both routes

Why it matters

Knowing that a simplified route never means simplified GMP stops sites lowering their controls for traditional products.

Practice: Practice: Herbal medicines in EU law · 3 questions

Opens with two companies buying the same dried chamomile: a herbal tea maker in London, for whom the cut flowers are the medicine itself, and an extract maker in Frankfurt, for whom they are a starting material for an active substance. You then work through the Annex 7 table and its notes: GACP for cultivation and collection, Part II or Part I for cutting, drying and extraction, and Part I for the finished medicine, and why some steps can be part of the harvest itself. The module shows that the use decides the rules, not the plant, and points to Annex 2 for genetically modified plants. You see how JKL Pharma classified its senna chain, through to tablet making in Mumbai under Part I. It ends with four signs of a sound classification and a recap.

What you will be able to do

• Apply the Annex 7 table to classify each step in a herbal chain
• Explain why the use of a material decides which rules apply
• Check that each supplier is audited against GACP or GMP correctly

Why it matters

Classifying each step correctly tells you which rules, inspections and records apply, before an inspector asks.

Practice: Practice: From field to product: which practice applies · 3 questions

Starts with a herbal importer in Madrid whose new grower had a GACP certificate and compliant certificates of analysis, yet an audit at harvest found a toxic weed at the field edge and leaves drying on bare ground by a road. You then learn Annex 7 point 7: use compliant herbal starting materials, keep audit records and make sure suppliers follow GACP. The module walks the GACP guideline from seeds to storage: clean soil, wild collection by people who can tell lookalike species apart, harvesting, and drying in thin layers off the ground. It covers field records with location, dates and quantities, written agreements, and expert audits timed for real risks. It ends with four signs of control, findings closed before the next lot, and a recap.

What you will be able to do

• Explain what the GACP guideline covers from seeds to drying
• Plan field audits at the time when real risks can be seen
• Check that every delivery traces back to a field record

Why it matters

Auditing the field, not just the file, finds the risks that perfect paperwork from a grower can hide.

Practice: Practice: GACP and the herbal supply chain · 3 questions

Opens at a chamomile cream maker in Milan where moths in one incoming lot spread through the general warehouse, several lots were rejected and herbs were moved to their own sealed rooms. You then work through the six points of Annex 7 on storage, production areas and equipment: herbal substances stored apart in aerated, clean areas, quarantined and approved lots in separate closed rooms, and special conditions provided and monitored. You see how JKL Pharma laid out its herbal store at the Mumbai site, records its storage conditions day by day, and uses a specialist pest control contractor. The module covers dust captured at its source with extraction and air pressures, waste bins, and equipment and filters compatible with the solvent. It ends with four signs of control and a recap.

What you will be able to do

• Apply the Annex 7 storage rules for herbal substances
• Check pest control records and dust capture in herbal areas
• Explain why equipment and filters must suit the extraction solvent

Why it matters

Storing herbs as living materials prevents infestations and dust that can spread to other products and force rejections.

Practice: Practice: Premises and equipment · 3 questions

Starts with a herbal tea maker in London whose own microscopic examination and distinctive identity test found a cheaper mint species mixed into peppermint leaf, despite a certificate that met every limit. You then work through Annex 7 point 8 item by item in three groups. What the plant is and where it comes from: binomial scientific name and author, source, plant part and drying system. How we know it is the right plant: description, microscopic examination, identity and distinctive tests, and a reference specimen. Whether it is clean and potent: water, assay, pesticides, microbes and toxins, metals, foreign matter and any treatment. You see JKL Pharma's specification for senna leaflets built line by line, with its reference specimen. It ends with four signs of a sound specification and a recap.

What you will be able to do

• Write a herbal substance specification that follows Annex 7 point 8
• Choose identity tests that catch lookalike substitutes
• Check that every contaminant group is covered or justified

Why it matters

A full specification lets you reject a substituted or contaminated lot before it reaches production, whatever the certificate says.

Practice: Practice: The herbal substance specification · 3 questions

Opens at an ivy leaf syrup maker in Paris where stones and a piece of glass were found in a sack only when the mill rattled, because receipt sampling had covered just a few containers. You then learn what processing instructions must describe, including drying times and temperatures and particle size control. The module covers examining each container for adulteration, substitution, foreign matter and decay, with a record of who examined each sack and when, trained eyes and the reference specimen, and removing foreign matter by security sieving. Extraction instructions fix the solvent, here ethanol and water at the dossier ratio, the time, temperature and concentration steps, and record drying method, end point and yield. It ends with four signs of control, such as flat assay results across harvests, and a recap.

What you will be able to do

• Examine every container for adulteration, substitution and decay
• Apply security sieving and screen checks to each lot
• Check that extraction instructions fix solvent, time and temperature

Why it matters

Looking inside every container protects equipment and product from stones, glass and decay that sampling a few would miss.

Practice: Practice: Processing and extraction · 3 questions

Starts at a valerian tablet maker in Amsterdam where one scoop from the top of a few sacks missed the soil and fines that had settled to the bottom during transport, and the extract ran low in assay. You then learn why heterogeneous plant material needs a plan saying which containers, where in each container and how much, with increments from the top, middle and bottom. The module shows the sampling record: which sacks, which depths, by whom and when. It covers keeping a reference sample, unmilled samples of material that will be powdered, a reference specimen for each plant and finished product samples under Annex 19. It ends with quality control expertise shown with blind samples, methods kept in line with current EU guidance and monographs, and a recap.

What you will be able to do

• Plan herbal sampling that covers the whole of each container
• Explain which reference samples and specimens to keep
• Check that analysts have shown their herbal expertise

Why it matters

Careful sampling by skilled people gives results that describe the whole lot, not just the cleanest pieces on top.

Practice: Practice: Sampling and quality control · 3 questions

Opens with the EMA herbal committee's work on pyrrolizidine alkaloids: its May 2016 statement accepting 1.0 microgram a day for a transitional period while producers moved towards 0.35, the January 2019 extension, and the European Pharmacopoeia chapter 2.8.26 adopted in November 2020. You then learn the upstream controls for these weeds, including a careful harvest. The module covers the other contaminants Annex 7 names: pesticides, mycotoxins from moulds when plants are harvested wet or dried slowly, toxic metals, smoke residues, microbes and any treatment, plus adulteration for weight. You see how JKL Pharma maps each senna contaminant to an upstream control and a test, and traces a failure to a toxic weed at a field edge. It ends with the ALARA principle and a recap.

What you will be able to do

• Explain the EMA approach and limit for pyrrolizidine alkaloids
• Map each herbal contaminant to an upstream control and a test
• Trace a contaminant failure back to its field and fix it there

Why it matters

Preventing contamination in the field and confirming it in the laboratory keeps toxins out of the medicine rather than finding them late.

Practice: Practice: Contaminants: from weeds to aflatoxins · 3 questions

Follows one senna lot through six stages: growing and harvest at a contract farm in southern India, drying and cutting at the farmers' cooperative under GMP Part II, receipt, examination and sampling at the Mumbai site with increments from top, middle and bottom, extraction into a dry extract, tableting and packing, then EU testing and certification by the Qualified Person in Dublin. You see how records and lot numbers link every stage, how rejected sacks are recorded against the supplier, and why the Qualified Person needs the entire supply chain documented with audit reports. The module covers what inspectors focus on and a readiness checklist for your own site. It ends with a course recap and the final exam, with its 60% mark, one retake and Certificate of Completion.

What you will be able to do

• Trace a herbal lot from field to release through its records
• Use a readiness checklist to review your own herbal site
• Explain what the Qualified Person needs before certifying a batch

Why it matters

Being able to trace any tablet back to its field is what an inspector looks for and what a recall depends on.

Practice: Practice: Putting it together: a lot, field to release · 3 questions