Biologics and ATMP

In brief

Biological medicinal products are manufactured with living cells or from biological material. They include therapeutic proteins and antibodies, which are mostly produced in cell cultures or microbial systems. A separate group are advanced therapy medicinal products (ATMPs): gene therapy medicinal products, somatic cell therapy medicinal products and tissue-engineered products. In these products, cells or genetic material are themselves the active substance.

Because such products are defined above all by their manufacturing process, their quality depends more on the process than with chemical active substances. Contract manufacturers, often called CDMOs, take over cell line development, cell banks, cultivation, purification, formulation and filling, or for ATMPs the entire manufacture up to the patient-specific batch.

Who needs this

Biotech companies and developers without their own GMP facilities for cell culture, viral vectors or cell therapy, from the first trial to commercial supply.

Legal basis

Manufacturing authorisation under Section 13 of the German Medicines Act (AMG) in consultation with the competent higher federal authority, the EU GMP Guide with Annex 2, and Part IV for ATMPs.

Typical scope

Cell banks, upstream and downstream processing, viral clearance, formulation, sterile filling, testing and, for ATMPs, transport and release per patient.

What matters

Control of the starting material, viral safety, comparability after process changes and a release concept that fits the shelf life.

When you need this

Facilities for biological manufacturing are expensive, need specialised staff and are additionally subject to genetic engineering law when genetically modified organisms are used. Many biotech companies therefore outsource manufacturing from the start. Typical occasions are the production of the first clinical trial material, the move to a larger-scale process before later trials and securing commercial supply through a second site. For autologous cell therapies, which are made from the patient’s own cells, the logistics between hospital and manufacturing are added.

Legal basis and rules

The manufacturing authorisation is granted by the competent Land authority (Länder). For sera, vaccines, allergens, advanced therapy medicinal products and medicinal products produced by genetic engineering, it decides under Section 13(4) AMG in consultation with the competent higher federal authority. Section 77 AMG determines which authority that is: the Paul-Ehrlich-Institut (PEI) is responsible for, among others, sera, vaccines, blood and tissue preparations, allergens and ATMPs, and the BfArM for everything else. Under Section 4(3) AMG, sera also include medicinal products with antibodies, antibody fragments or fusion proteins with a functional antibody component as the active substance.

Section 13(4) and Section 77 AMG

Authorisation from the Land authority in consultation with the higher federal authority. The PEI is responsible for sera including antibodies, vaccines, allergens and ATMPs.

EU GMP Guide, Annex 2

Manufacture of biological active substances and medicinal products, in force since 26 June 2018. Does not apply to ATMPs.

EU GMP Guide, Part IV

Separate GMP guideline for ATMPs, in force since 22 May 2018, for authorised ATMPs and for ATMPs in clinical trials.

ICH Q5A(R2)

Viral safety of biotechnology products derived from cell lines of human or animal origin, applicable in the EU since 14 June 2024.

ICH Q5B to Q5E

Analysis of the expression construct, stability testing, derivation and characterisation of cell substrates, and comparability after changes in the manufacturing process. Q5C is to be merged into the revised ICH Q1, which is still in draft as of November 2026.

Section 8 GenTG

Under the German Genetic Engineering Act (GenTG), genetic engineering work only in genetic engineering facilities, with notification, registration or approval depending on the safety level.

Annex 2 for proteins and antibodies

Annex 2 supplements Part I and Part II of the EU GMP Guide for the full range of biological medicinal products with the exception of ATMPs. Part A contains general requirements, from the control of seed lot and cell bank systems to filling and testing, and Part B contains additional guidance on specific product types. For biological active substances, Part II applies primarily up to the point immediately before sterilisation, and Part I for the subsequent steps. Many proteins and antibodies do not tolerate heat sterilisation, so the finished medicinal product is filled aseptically, to which Annex 1 applies.

Part IV for ATMPs

ATMPs are not covered by Annex 2 but by Part IV, to which Section 3 of the German Ordinance on the Manufacture of Medicinal Products and Active Substances (AMWHV) also refers. It is based on a risk-based approach that takes into account the specific features of these products, such as small batches, starting material from individual patients and short shelf life. Every manufacturing site in the EEA needs at least one Qualified Person (QP). Because of short shelf life, a batch may be released in stages, first on the basis of the results available and finally once all tests are complete. This procedure must be laid down in writing. ATMPs used under the hospital exemption must be manufactured to equivalent quality standards. In Germany, Section 4b AMG governs these cases and requires an authorisation from the higher federal authority for supply to others.

Important

Part IV is being revised. According to a 2025 EMA concept paper, it is mainly to be aligned with Annex 1, which entered into force in 2023, for example on the contamination control strategy, cleanrooms, isolators, closed systems and single-use systems. A draft was planned for September 2026 but was not yet available in November 2026, so the 2017 version still applies. For an ATMP project, clarify how the manufacturer is preparing for the changes.

How the collaboration works

For outsourced activities, Chapter 7 of the EU GMP Guide and, for ATMPs, Section 13 of Part IV require a written contract that sets out the responsibilities of both parties, including for quality defects and traceability.

Describe the project

Product type, expression system or cell type, stage of development, quantities or patient numbers, target markets and trial timeline.

Audit and selection

The audit covers cell banks, segregation of products and organisms, handling of viruses and adventitious contamination, testing capacity and, for ATMPs, the logistics between hospital and manufacturing.

Contract and quality agreement

They set out responsibility for starting material, testing, deviations, changes, traceability and certification by the Qualified Person.

Process transfer

Cell line or vector, process description and methods are transferred. For later changes to the process, the comparability of the product must be demonstrated under ICH Q5E.

Manufacturing and release

Manufacture according to plan or per patient, testing, certification and, for ATMPs, staged release where applicable according to the defined procedure.

What to look for when selecting a manufacturer

Questions to ask the provider

Does the manufacturing authorisation cover your product type, and is the genetic engineering facility approved for the required safety level?

Which expression systems, cell types or vectors does the manufacturer have experience with?

How are master and working cell banks established, stored and tested?

Which viral clearance steps and which virus tests are established?

How are different products and organisms segregated in the facility?

Which analytical testing is done in-house, and what is subcontracted?

For ATMPs, is there a written procedure for release before all tests are complete?

How is the cold chain between hospital, manufacturing and administration organised?

Frequently asked questions

Is the PEI or the BfArM responsible for antibodies? +

Under Section 4(3) AMG, medicinal products with antibodies, antibody fragments or fusion proteins with a functional antibody component count as sera, and under Section 77(2) AMG the PEI is responsible for sera. For other proteins produced by genetic engineering, such as hormones or enzymes, the BfArM is responsible under Section 77(1) AMG. Exceptions are vaccines and allergens produced by genetic engineering and blood components produced by genetic engineering, such as recombinant coagulation factors, for which the PEI is responsible.

Does Annex 2 also apply to cell and gene therapy products? +

No. Annex 2 expressly excludes ATMPs. They are covered by Part IV of the EU GMP Guide, to which Section 3 AMWHV also refers in Germany.

May an ATMP be administered before all tests are complete? +

For short shelf life, Part IV allows release in stages: a first certification based on the data available and a final one once all results are in. The procedure and the handling of results that deviate later must be laid down in writing.

What does a process change mean for a biological product? +

Because the process shapes the properties of the product, the manufacturer must show under ICH Q5E that the product is comparable before and after the change. Depending on its extent, the change may also affect the marketing authorisation or the clinical trial authorisation.

Sources

Every statement in this text was checked against these primary sources (as of 10.11.2026). Laws, guidelines and authority websites, no advertising.

Company	Location	EvidenceQuote from the company’s website (German)	Credentials
Bibitec GmbH & Co. KG BIBITEC GmbH & Co. KG in Bielefeld is a contract manufacturer of biological active substances. It produces proteins and antibodies using mammalian cells under GMP, up to Phase III.	Bielefeld Nordrhein-Westfalen	Evidenced „BIBITEC ist ein Auftragsproduzent (CMO) für die GMP-gerechte Wirkstoffproduktion mit Hilfe von Säugerzellen.“ Source · 10 Nov 2026 ↗	Manufacturing authorisation GMP certificate
Celonic Deutschland GmbH & Co. KG	Heidelberg Baden-Württemberg	Evidenced „Celonic offers end to end drug substance development and manufacturing solutions for monoclonal antibodies, bispecifics and other complex molecules.“ Source · 10 Nov 2026 ↗	Manufacturing authorisation GMP certificate
FamiCord AG FamiCord AG in Leipzig stores umbilical cord blood and tissue for families and partners, and as a CDMO it offers cGMP manufacture of cell-based ATMPs. Its focus is on perinatal stem cells.	Leipzig Bayern	Evidenced „As a CDMO, we specialize in the development of cell therapy ATIMPs, including process development / optimization, tech transfer, cGMP manufacturing“ Source · 10 Nov 2026 ↗	Manufacturing authorisation
IDT Biologika GmbH IDT Biologika GmbH in Dessau-Roßlau is a contract manufacturer of vaccines, viral vectors and sterile injectables. It offers process development, drug substance production, aseptic filling and packaging for third parties.	Dessau Rosslau Sachsen-Anhalt	Evidenced „IDT Biologika, Teil von SK bioscience, unterstützt Pharma- und Biotech-Unternehmen dabei, innovative Therapien schneller zu den Patienten zu bringen.“ Source · 10 Nov 2026 ↗	Manufacturing authorisation GMP certificate
JEmedis GmbH JEmedis GmbH, based in Luckenwalde, is a CDMO offering contract manufacturing of biologics, pilot batches and aseptic fill and finish in small batches. The company also markets its own urology and oncology products.	Luckenwalde Brandenburg	Evidenced „Unterstützung bei der Entwicklung und Optimierung von Herstellungsprozessen für Biologika basierend auf einem bestehenden Herstellungsdesign sowie die Lohnherstellung von Pilotchargen“ Source · 10 Nov 2026 ↗	Manufacturing authorisation GMP certificate
Pharma-Zentrale GmbH Pharma-Zentrale GmbH in Herdecke is a family-owned group offering GMP-compliant contract manufacturing, fermentation and active pharmaceutical ingredient production, as well as its own probiotic and herbal medicinal products.	Herdecke Nordrhein-Westfalen	Evidenced „BBT Biotech ist spezialisiert auf die vertragliche Entwicklung und GMP-Herstellung biopharmazeutischer Wirkstoffe.“ Source · 10 Nov 2026 ↗	Manufacturing authorisation GMP certificate
Probiogen AG ProBioGen AG, based in Berlin, is a CDMO for biopharmaceuticals, offering cell line development, process development and GMP manufacturing of proteins, antibodies and viral vectors for biotech and pharmaceutical clients.	Weissensee Berlin	Evidenced „We provide comprehensive CDMO services for biologics and advanced therapies paired with stellar technologies to bring your candidate to clinic“ Source · 10 Nov 2026 ↗	Manufacturing authorisation GMP certificate
Rentschler Biopharma SE Rentschler Biopharma SE in Laupheim is a CDMO for biopharmaceuticals, with a focus on process development, cGMP manufacture of recombinant proteins and analytical development for customers worldwide.	Laupheim Baden-Württemberg	Evidenced „Wir sind Spezialisten für die Entwicklung, Optimierung und Charakterisierung von Herstellungsprozessen rekombinanter Proteine von der DNA bis hin zur Drug Substance.“ Source · 10 Nov 2026 ↗	Manufacturing authorisation GMP certificate