What is lot genealogy, and what forward and backward traceability do GMP rules require?

1What lot genealogy means.

FDA’s definitions set the idea. A lot number is “any distinctive combination of letters, numbers, or symbols” from which “the complete history of the manufacture, processing, packing, holding, and distribution of a batch or lot” can be determined. A batch is a quantity “produced according to a single manufacturing order during the same cycle of manufacture”, and a lot is a batch or an identified portion of one.¹ In EMA’s GMP questions and answers on medicinal gases, traceability is “the ability to retrieve the history of the manufacturing and distribution operations of a batch”, and its data should allow efficient investigation and recalls.²

Genealogy has two directions. Backward traceability starts from a batch, a complaint or a failed result and finds the component lots, equipment and records behind it. Forward traceability starts from a component lot, such as one a supplier has recalled, and finds every batch that used it and every consignee that received those batches. Both rely on the same links, recorded at receipt, dispensing, production, packaging and shipment.³

2What 21 CFR 211 requires.

Part 211 builds traceability from records kept at each point where material changes hands.³

Investigations rely on the forward links. Under 211.192 an unexplained discrepancy or failure must be thoroughly investigated, and the investigation “shall extend to other batches of the same drug product and other drug products that may have been associated with the specific failure or discrepancy”.³

3What EU GMP adds for the supply chain.

EU GMP Chapter 4 asks for the same links in its own words. The batch processing record holds the batch number and quantity of each starting material actually weighed, including any recovered or reprocessed material; receipt records hold the manufacturer’s batch number and the batch number assigned after receipt; and distribution records for each batch should “facilitate recall of any batch”.⁴

The EU then reaches back up the supply chain. Chapter 5, section 5.29, in operation since 1 March 2015, says supply chain traceability for active substances should be established, with the risks “from active substance starting materials to the finished medicinal product” formally assessed and periodically verified.⁵ Annex 16, in operation since 15 April 2016, makes it part of certification: “the entire supply chain of the active substance and medicinal product up to the stage of certification” is documented and available to the Qualified Person, preferably as a diagram that includes subcontractors of critical steps.⁶

EMA’s questions and answers explain what those records should show: every entity, “including suppliers and outsourced activities, involved in the manufacture of a specific batch of the drug product, in line with the registered supply chain”, available in time for defect investigations and recalls. On batch numbers, they note that a bulk batch packed as several finished batches normally shares an element of its number with them, and that GMP inspectors regard completely unrelated numbers as an undesirable practice to avoid, partly because they can confuse a recall and make it ineffective.²

For active substances, ICH Q7 asks that a blended batch’s record allow traceability back to the individual batches in the blend, and that agents, brokers, distributors, repackers and relabellers “maintain complete traceability” of what they distribute, including the original manufacturer and its batch number.⁷

4Cell therapies and tissues need tracking both ways.

For advanced therapy medicinal products, the EU’s ATMP GMP guidelines, adopted on 22 November 2017, call for a system for “the bidirectional tracking of cells/tissues contained in ATMPs from the point of donation, through manufacturing, to the delivery of the finished product to the recipient”, in place from the first clinical batches. It covers raw materials and substances that touch the cells, and its data, including the donation code, the manufacturer’s internal code and critical raw material batch numbers, are kept for at least 30 years after the product’s expiry date.⁸

In the US, 21 CFR 1271.290 requires establishments that handle human cells, tissues and cellular and tissue-based products to track each one from the donor to the consignee or final disposition and back, using a distinct identification code that may not include a person’s name, social security number or medical record number.⁹

5Package-level tracing after release in the US.

Once a finished product enters US distribution, the Drug Supply Chain Security Act of 2013 adds tracing between trading partners. FDA describes it as “an interoperable and electronic way to identify and trace certain prescription drugs at the package level”.¹⁰ A manufacturer affixes a product identifier to each package and homogenous case: the National Drug Code with a unique serial number, the lot number and the expiry date, in human-readable and machine-readable form. When it transfers ownership, it passes on the transaction information, history and statement, and keeps them, with lot-level information, for at least six years.¹¹

6How it runs in Seal.

In Seal, each physical container carries its quantity, status, location history and actual use as transactions, and the execution record keeps the exact container and quantity consumed. From a supplier lot or container, the inventory blueprint describes tracing forward through samples, tests, batches, intermediates, finished products, shipments, retained samples, remaining stock, returns and destruction, and from a batch backward to the containers, approvals, locations, excursions and movements behind it. A split gives each child container its own identity linked to the parent and the split event, as the lot splitting guide shows.

Neil, Seal’s AI agent, can trace a material lot through receipts, consumption and intermediate splits and draft a genealogy assessment that keeps unresolved links in view. Quality determines product impact and any market action; recorded consumption identifies candidates, it does not authorise a recall.