Biosimilars and reference biologics in named-patient supply

Named-patient requests for biologics often arrive with a simple instruction: supply this antibody, insulin or growth factor for one patient. Behind that instruction sits an important choice. Does the prescriber want the original reference product, a particular biosimilar, or any product with the same active substance? With small molecules the answer is often flexible. With biologics it is not, because each manufacturer's product is made in living cells by its own process, and regulators approve biosimilars product by product.

This guide explains how the main regulators define biosimilars, who decides on substitution, why traceability matters and how to write a precise request. It does not give clinical advice. The choice between a reference product and a biosimilar belongs to the prescriber.

How regulators define biosimilars

The definitions share one idea: a biosimilar is compared with a reference product that the same regulator has already approved.

EMA's biosimilar overview gives the EU definition. FDA's review and approval page gives the United States definition and the meaning of interchangeability. WHO's Guidelines on evaluation of biosimilars, published in April 2022, replace the earlier WHO guidance on similar biotherapeutic products in Technical Report Series No. 977. They apply to well-characterised products such as recombinant therapeutic proteins and exclude vaccines and plasma-derived products.

The practical consequence is simple. A biosimilar approved by one regulator has not necessarily been assessed by another. A product approved in India, for example, may have no EU or United States approval at all, and a product approved as a biosimilar in the EU may be sold under a different name or presentation elsewhere.

Interchangeability and who decides

In September 2022 EMA and the Heads of Medicines Agencies stated that biosimilars approved in the EU are interchangeable from a scientific viewpoint. The same EMA page notes that Member States still decide which biological medicines are available for prescribing and whether automatic substitution at pharmacy level is allowed, and that any interchange should follow careful consideration of the product information. In the United States, only products FDA has designated as interchangeable may be substituted at the pharmacy without the prescriber's intervention, and state laws add their own conditions.

Named-patient supply sits outside these routine pharmacy rules. The medicine is unregistered in the destination country, a licensed local party applies for a permit or notification, and the prescriber justifies the specific product. That leads to three working rules:

• The prescriber names the product, ideally by brand and manufacturer as well as by international non-proprietary name.
• The supplier does not substitute. If the named product is unavailable, the supplier reports that and lists alternatives for the prescriber to consider.
• A change of product usually means a new decision by the prescriber and, in many countries, a new permit, as explained in how named-patient supply works.

Naming and traceability

Adverse reactions to biologics can be linked to one manufacturer, one process change or one batch. EU law addresses this directly. Directive 2010/84/EU, which amended Article 102 of Directive 2001/83/EC, requires Member States to take measures so that any biological medicine in a suspected adverse reaction report is clearly identified, with due regard to its name and batch number.

FDA takes a naming approach. Its January 2017 guidance on nonproprietary naming adds a suffix of four lowercase letters, with no meaning of its own, to the core name of biological products. FDA explains that the suffix supports pharmacovigilance and helps prevent inadvertent substitution of products not determined to be interchangeable.

For named-patient supply, traceability depends on the paperwork carrying the same identifiers from end to end:

Writing a precise request

1. State the international non-proprietary name, brand and manufacturer the prescriber has chosen.
2. Give the strength and presentation, for example vial, pre-filled syringe or pen, since presentations differ between markets.
3. Name the acceptable market of origin, such as an EU pack, a United States pack or an Indian pack, or say that the prescriber accepts any listed option.
4. Say whether the prescriber has approved any alternative products, and attach that decision.
5. Give the quantity, the required remaining shelf life and the date needed.
6. Confirm the destination route and the consignee, using the country import guides for the rules.
7. Ask for the batch number and certificate of analysis to be confirmed before the permit is filed, so the permit and shipment match.

The quote request form collects these details, and how to prepare a medicine sourcing request explains each field.

When the prescriber accepts more than one product

Sometimes the prescriber is willing to consider either the reference product or one or more named biosimilars, for example because one is in short supply. In that case it helps to ask the supplier for a side-by-side quote rather than a single offer. Each option should show the brand, manufacturer, approving regulator, market of origin, presentation, available batch and remaining shelf life, and lead time. Prices and lead times can differ widely between options, as explained in medicine pricing and lead times.

The prescriber then chooses, and the permit or notification is filed for that product. Many routes tie the approval to the specific medicine, dose and quantity named in the application, so an approval for one brand should not be assumed to cover another. The supplier's role is to describe each option accurately. It should not rank them or suggest that one works better than another, since that is a clinical judgement for the treating team.

Cold chain and handling

Many biologics are labelled for storage at 2 to 8°C, and some must not freeze. That makes the shipping lane part of the product decision. A pack that reaches the hospital after an unrecorded excursion may be unusable, whatever its approval status. Before dispatch, agree the packaging qualification time, the route and hubs, who monitors the logger and what happens after an excursion. The guides on cold-chain shipping of biologics from India and temperature excursions in transit cover the details, and the cold-chain transit checker compares packaging time with transit time.

Reference products sourced from India

Some multinational reference biologics are sold in India in packs made for the Indian market, and India also has its own approved biosimilars. Either can be relevant for a named patient, but each raises a different question for the destination regulator. An Indian pack of a reference brand may differ from the EU or United States pack in labelling, presentation or manufacturing site. An India-approved biosimilar may have no approval from EMA or FDA. The hospital should ask its regulator which of these it will accept before the request is finalised, and the exporter should state the market of origin and manufacturer plainly on the quote.