No single document settles an import. The paperwork answers three separate questions: whether each party is authorised, whether the manufacturer's system is trusted, and what happened to this batch. A certificate of analysis answers only the third. A certificate of pharmaceutical product speaks to the first two and says nothing about the batch.
The three questions the paperwork answers
What documents to check before importing medicines is usually answered with a list. Invoice, packing list, transport document, certificate of analysis, GMP certificate, certificate of pharmaceutical product. The list is not wrong. It is not a method either, because it does not say what each document is evidence of, and these documents are evidence of very different things.
The paperwork answers three separate questions. Whether each party is allowed to act. Whether the manufacturer's system is trusted. What happened to the batch on the pallet. Most avoidable receiving failures come from settling one of those questions with a document that answers a different one.
WHO sets out the documents for border and customs clearance in Technical Report Series No. 1019, Annex 5, Guidelines on import procedures for medical products. Section 6.1 introduces them as documents that can be considered, not as a fixed set, and section 4.1 places the requirement itself in national and regional legislation. The binding list in any market is the one that market's authority publishes. What follows is what the widely copied frameworks ask for, and what each document can carry.
Documents that say who may act
The first group establishes standing. It records who is permitted to import, to distribute, and to place the product on the market. None of it speaks to quality.
WHO's annex puts two of these at the front. Section 4.3 says the import of medical products should be undertaken by an importer or agency authorised by the national regulatory authority. Section 5.1 says that only products approved by appropriate documentation to be duly registered or authorised, as appropriate for marketing, should be cleared. Section 5.2 asks the authority to publish an updated list of both, and asks for close collaboration to confirm there are no restrictions, temporary suspensions or withdrawals in force. An authorisation that was valid when the order was placed is not evidence that it is valid on the day the goods arrive.
The EU framework splits the same question by activity, which is why its names differ. Article 40(1) of Directive 2001/83/EC makes manufacture subject to an authorisation, and Article 40(3) requires that same authorisation for imports coming from third countries, so an importer there holds a manufacturing authorisation rather than a separate import licence. Article 80(b) requires a wholesale distributor to obtain supplies only from persons holding a distribution authorisation or exempt from holding one, and Article 80(e) and 80(f) require a record of every transaction, including the batch number for products bearing safety features, kept for five years.
| Document | Issued by | What it evidences | What it does not evidence |
|---|---|---|---|
| Importer authorisation | The regulatory authority of the importing country | That this importer may import medical products into this market | Nothing about the product, the manufacturer or the consignment |
| Marketing authorisation or registration | The regulatory authority of the importing country | That this product is authorised for sale in this market | Not that the goods in front of you are that product, and not that the authorisation is still in force today |
| Manufacturing and import authorisation | The competent authority of an EU or EEA state | That the holder may import medicinal products from outside the EU and EEA and carry out importation activities | Not that any particular batch has been imported, tested or released |
| Wholesale distribution authorisation | The competent authority of the supplier's country | That the supplier may distribute medicinal products by wholesale | Not that the supplier manufactured, tested or released anything |
Documents that speak for the manufacturer's system
The second group speaks for a site and a system, not for a consignment. These are the documents most often over-read.
A GMP certificate records that a named site was found to comply at a stated inspection, within a stated scope. The scope carries as much weight as the finding. Annex 21 of the EU GMP guide notes in passing that an EU GMP certificate may restrict activities to specific manufacturing units or buildings at a third country site, which is a reminder that a certificate naming a company is not a certificate covering everything that company makes.
The certificate of pharmaceutical product is the document most often treated as a quality guarantee, and WHO says plainly that it is not one. The model quality assurance system for procurement agencies states that a CPP is not a guarantee of compliance with GMP, that participation in the WHO Certification Scheme is a voluntary process, and that there is no formal assessment or evaluation of the medicines regulatory authorities entering the scheme. It adds that reliance on the CPP alone is in some cases not recommended, and that the scheme is an administrative tool, reliable only where the relevant authority has an established system known to comply with acceptable standards. The same document says the same of ISO certification, which it describes as neither an assurance of compliance with WHO GMP nor a substitute for establishing it.
That does not make a CPP worthless. It makes it a statement about registration and inspection status in the exporting country, issued by that country's authority, and checkable as such. WHO publishes the list of government organisations authorised to sign and issue a CPP, and Annex 5 section 5.4 says an authority receiving a CPP can use that list to check whether the certificate came from the organisation entitled to issue it. That is a real check, and it is a check on provenance rather than on quality.
| Document | Issued by | What it evidences | What it does not evidence |
|---|---|---|---|
| GMP certificate | The inspecting authority | That a named site was found compliant at a stated inspection, within a stated scope | Not that this batch was made under those conditions, and not activities outside the stated scope |
| Certificate of pharmaceutical product | The competent authority of the exporting country, in the WHO scheme's format | The product's marketing authorisation status in the exporting country and the stated GMP status of the manufacturer | Not a guarantee of GMP compliance, in WHO's own words, and nothing at all about the batch supplied |
| Written confirmation for an active substance | The competent authority of the exporting third country | That the plant's GMP standards are at least equivalent, that it is under regular, strict and transparent controls including repeated and unannounced inspections, and that non-compliance findings are reported without delay | Not a batch document, and not a statement about the material actually shipped |
The written confirmation, precisely
Active substances have a document of their own, and its content is set out in Article 46b(2)(b) of Directive 2001/83/EC rather than left to practice. The written confirmation is issued by the competent authority of the exporting third country and attests three things: that the standards of good manufacturing practice applicable to the plant are at least equivalent to those laid down by the Union, that the plant is subject to regular, strict and transparent controls and to effective enforcement including repeated and unannounced inspections, and that findings of non-compliance are supplied to the Union without delay.
Two qualifications sit in the same article. Article 46b(3) removes the requirement where the exporting country appears on a list maintained under Article 111b. Article 46b(4) allows a time-limited waiver where a plant has been inspected by a Member State and found compliant. Both turn on published material that changes, so the current list and the current status are the things to read, not a country list repeated in an article.
Documents that speak for this batch
The third group is the only group that says anything about the goods on the pallet. It is also the group where the certificate of analysis sits, and where its limits are easiest to state.
WHO's Annex 5 section 6.1 names a batch-release certificate issued by the manufacturer, and an invoice, bill or delivery slip for the batch carrying the product name, batch number, quantity and expiry date. Section 8.4 adds a rule for starting materials that is worth reading twice: materials purchased and imported from third-party vendors should be accompanied by a certificate of analysis from the original manufacturer. A certificate re-issued on a trader's letterhead is a copy of a claim, not the claim itself.
| Document | Issued by | What it evidences | What it does not evidence |
|---|---|---|---|
| Certificate of analysis | The manufacturer that tested the batch | The results obtained on that batch against the specification applied, with the methods and dates | Not that the goods delivered are that batch, and not a release decision in the importing market |
| Batch release certificate or warranty | The manufacturer | That the manufacturer released the batch against its own specification | Not release in the importing market, and not a check by anyone independent of the maker |
| Control report signed by a qualified person | The qualified person of an EU or EEA authorisation holder | That the batch underwent full qualitative analysis and quantitative analysis of the active substances in a Member State, against the marketing authorisation | It belongs to the EU and EEA framework, and does not travel to markets outside it |
| Invoice, bill or delivery slip | The supplier | Product name, batch number, quantity and expiry date for this consignment | Nothing about quality; it is the document the other documents are matched against |
| Transport and temperature records | The carrier or the supplier | The conditions the consignment was held at in transit | Not the condition of the batch at manufacture, and not what happened before collection |
Why the supplier's certificate is not the release document
Public document checklists collapse this distinction. It is the one worth carrying away.
Article 51(1)(b) of Directive 2001/83/EC puts it in one sentence. For medicinal products coming from third countries, irrespective of whether the product was manufactured in the Union, the qualified person secures that each production batch has undergone in a Member State a full qualitative analysis, a quantitative analysis of at least all the active substances, and all the other tests or checks necessary to ensure quality in accordance with the marketing authorisation. The testing happens on arrival, in the importing territory, and the supplier's certificate is not a substitute for it. Article 51(2) allows relief from those controls only where arrangements have been made with the exporting country, which is what a mutual recognition agreement is for.
Annex 21 then says what the supplier's certificate is for. Under the product quality review in section 3.2, the analytical results from importation testing should be compared with those in the certificate of analysis generated by the third country manufacturer, and any discrepancies or out of trends documented and investigated. The certificate is the benchmark the importer's own results are read against. That is a real and important job, and it is not the job of deciding that the batch may be sold.
The output of the qualified person's decision is a separate document. Article 51(1) says batches that have undergone those controls in one Member State are exempt from repeating them elsewhere in the Union when accompanied by the control report signed by the qualified person, and Article 51(3) requires the certification to be recorded and kept for at least five years. The good distribution practice guidelines close the loop at section 5.4: batches should not move to saleable stock before assurance that they are authorised for sale, and for batches coming from another Member State the Article 51(1) control report, or equivalent proof of release, should be carefully checked by appropriately trained personnel. Two different documents, two different signatures, two different questions.
Checking the supplier before checking the documents
Documents are only as good as the party that produced them, which is why the good distribution practice guidelines put supplier qualification before procurement rather than after it. Section 5.2 asks for appropriate qualification and approval of suppliers prior to any procurement, controlled by a procedure, with the results documented and periodically rechecked.
The same section requires supplies to come only from persons holding a wholesale distribution authorisation or a manufacturing authorisation covering the product, and adds that a distributor receiving medicinal products from third countries for the purpose of importation must itself hold a manufacturing authorisation. Where goods come from another distributor, compliance and authorisation are to be confirmed, for example through the Union database. Where they come through a broker, the broker's registration is checked instead.
For a new contract with a new supplier the guidelines name four things to attend to during due diligence, and they read like a description of how a bad consignment is sold rather than a compliance formality:
- The reputation or reliability of the supplier.
- Offers of medicinal products more likely to be falsified.
- Large offers of medicinal products which are generally only available in limited quantities.
- Out-of-range prices.
The correspondence check on arrival
WHO's model quality assurance system for procurement agencies sets out what happens when the goods land, at section IV.3. Incoming materials and finished products are quarantined immediately on receipt until released, and a review of certificates of analysis is strongly recommended to confirm that what has been delivered is what was ordered and is certified by the manufacturer to meet specifications.
The check itself is a four-way correspondence, and it is the most useful sentence in the annex. Each incoming delivery is checked for correspondence between the order, the delivery note, the supplier's labels and the transport conditions. The consignment is examined for integrity of packages and seals and for uniformity of containers. Where a delivery comprises more than one batch, it is subdivided according to the supplier's batch number.
Two other frameworks add to the same moment. Annex 21 section 5.1.3 asks that ordering and delivery documentation clearly indicate the site the product was dispatched from, the site of physical importation, and the shipping details, including transport route, temperature monitoring records and customs documentation such as the packing list or the customs import declaration. WHO's Annex 5 section 7.1 asks that the size of the consignment be checked against invoices, bills or delivery slips, and notes that spelling errors, low-quality printing and other defects on the external package may be signs of a substandard or falsified product.
- Quarantine on receipt, and release only against a decision, not against the arrival of paperwork.
- Match four things, not two: the order, the delivery note, the labels on the goods, and the transport conditions.
- Split the delivery by the supplier's batch number, then confirm every batch has its own certificate.
- Read the packaging as evidence in its own right, including the printing.
A worked example
Take a consignment of 40 shipping cartons of a film-coated tablet, ordered on a single purchase order. The file that travels with it looks complete: a commercial invoice, a packing list, a certificate of pharmaceutical product, a GMP certificate for the manufacturing site, and a certificate of analysis. A checklist that asks only whether each document is present passes this consignment.
The correspondence check takes minutes and produces three findings. The packing list shows two batch numbers, 24 cartons of one and 16 of the other. There is one certificate of analysis and it carries the first batch number, so 16 cartons have arrived with no certificate at all. The rule that a delivery of more than one batch is subdivided by the supplier's batch number exists for exactly this, and here the paperwork was built for one batch and the pallet holds two.
The GMP certificate names the site correctly and is in date. Its scope covers oral liquids. The goods are tablets, so the certificate is evidence about a production line the consignment never touched. Nothing is forged and nothing is expired; the document simply does not reach the goods.
The certificate of analysis is issued on the letterhead of the trading company that sold the goods and reports results without naming the laboratory or the manufacturer that produced them. For a starting material WHO's position is explicit, that the certificate should come from the original manufacturer. For a finished product the same logic holds with less formal force: a certificate that cannot be traced to the party that did the testing is a transcription, and a transcription cannot be checked against anything.
None of those three findings needs a laboratory. All three are visible in the documents themselves, and all three survive a review that only asks whether the file is complete.
What none of these documents settles
Every document above is a record of something someone else did. A registration is a decision taken by an authority, a GMP certificate is the finding of an inspection on a particular day, a certificate of analysis is a report of tests performed by the maker on a sample of a batch. The consignment sitting in the warehouse is not any of those things, and the gap between the record and the goods is where substandard product enters a legal supply chain.
That gap is why the frameworks put physical checks and quarantine beside the document review rather than after it, and why the good distribution practice guidelines ask a distributor to use all means available to minimise the risk of falsified medicinal products entering the legal supply chain.
Two documents commonly listed beside these were left out on purpose. The certificate of suitability to a European Pharmacopoeia monograph and the active substance master file answer a narrower question about how an active substance is controlled, and they deserve their own comparison rather than a line in a table.
A complete file is where the receiving decision starts, not where it finishes. Documents narrow the question. They do not close it.
Definitions
- Certificate of analysis (CoA)
- The manufacturer's report of the tests performed on a batch and the results obtained, against the specification applied. WHO TRS 1019 Annex 5 section 8.4 asks that a starting material bought from a third-party vendor be accompanied by the certificate of analysis from the original manufacturer.
- Certificate of pharmaceutical product (CPP)
- A certificate in the format of the WHO Certification Scheme, issued by the competent authority of the exporting country, on the product's marketing authorisation and manufacturing status there. WHO TRS 986 Annex 3 states that a CPP is not a guarantee of compliance with GMP.
- Written confirmation
- The document required by Article 46b(2)(b) of Directive 2001/83/EC for imported active substances, issued by the competent authority of the exporting third country, attesting equivalent GMP standards, regular strict and transparent controls including unannounced inspections, and prompt reporting of non-compliance findings.
- Control report
- The record referred to in Article 51(1) of Directive 2001/83/EC, signed by a qualified person, showing that a batch has undergone the required analysis in a Member State. Batches accompanied by it are exempt from repeating those controls elsewhere in the Union.
- Good distribution practice (GDP)
- The standards governing wholesale distribution. Chapter 5 of the EU guidelines (2013/C 343/01) covers qualification of suppliers at 5.2 and receipt of medicinal products at 5.4, including the check of the Article 51(1) control report before stock becomes saleable.
- Supplier qualification
- The documented assessment and approval of a supplier before procurement. EU GDP section 5.2 requires it prior to any procurement, controlled by a procedure, documented and periodically rechecked, with named due-diligence signals for new suppliers.
Sources
- WHO Technical Report Series No. 1019 (2019), Annex 5: Guidelines on import procedures for medical products, World Health Organization (sections 4.1 to 4.3, 5.1, 5.2, 5.4, 6.1, 7.1 and 8.4)
- WHO Technical Report Series No. 986 (2014), Annex 3: WHO model quality assurance system for procurement agencies, World Health Organization (section II.2.4.5 on existing certificates, and section IV.3 on receipt of stock)
- Guidelines of 5 November 2013 on Good Distribution Practice of medicinal products for human use (2013/C 343/01), European Commission, Official Journal of the European Union (Chapter 5, sections 5.1, 5.2, 5.4 and 5.8)
- Directive 2001/83/EC on the Community code relating to medicinal products for human use, consolidated text, European Commission (Articles 40(1) and 40(3), 46b(2) to 46b(4), 51(1) to 51(3), and 80)
- EudraLex Volume 4, Annex 21: Importation of medicinal products, European Commission (sections 2.4, 3.2, 4.2, 5.1.3, 5.3 and 5.5; in operation from 21 August 2022)
Primary sources are cited in preference to summaries. Where a source is licensed (for example a pharmacopoeial monograph) the reference is given and the text is not reproduced.
PharmaTrust Team
Written and reviewed by the PharmaTrust team against the primary sources cited above. Corrections are published, never made quietly.
Why we built this →Spotted an error or a newer figure? We correct within a week: info@pharmatrust.tech.