Biologics and Biosimilars Regulation and Registration in Germany

Preparing for Biologics and Biosimilars Regulation in Germany? Here’s the part most people miss. A separate German process doesn’t really exist. Everything runs on the EU centralised procedure. EMA reviews the dossier and the Commission grants the actual authorisation. After that only Germany’s own regulators, PEI and BfArM, take over the national responsibilities. These include batch release, pharmacovigilance follow-up, inspections and national labelling review.

The article includes information on who regulates biologics in Germany, legal and compliance requirements, the whole registration process and documents, labeling, time and fee schedules and post-marketing surveillance obligations.

Regulatory Authority for Biologics and Biosimilars in Germany

No single regulator handles biologics in Germany. The job splits across EU bodies and two German federal institutes and figuring out which one to contact early saves real time.

Germany Biologics and Biosimilars Regulatory Requirements

Biologics Regulatory Requirements and Biosimilars Regulatory Requirements in Germany rest on two rulebooks before any dossier reaches a regulator. They are EU law and German national law. Missing either one causes rejection or delay.

At the EU level:

• Directive 2001/83/EC – general legal groundwork for human medicinal products.
• Regulation (EC) No. 726/2004 – It makes the centralised procedure mandatory for biologics made with certain biotechnology processes
• EudraLex Volume 4 – sets the EU Good Manufacturing Practice (GMP) guidelines that manufacturing sites are expected to follow. Compliance with these standards is verified through regulatory inspections before approval.

At the German level, there’s the Arzneimittelgesetz (AMG). It takes the EU’s rules and turns them into actual German law, covering things like manufacturing authorisation, wholesale distribution and national pharmacovigilance duties.

Then there is Section 32 AMG that says vaccines, sera and allergens can’t reach the German market until PEI has officially tested and released each batch. That’s a PEI responsibility and it doesn’t apply to biosimilars in general.

Manufacturing and distribution sites for Biologics and Biosimilars must follow Good Distribution Practice and pharmacovigilance duties from the day they are authorized. Serialization is also required for Biologics and Biosimilars under the European Union Falsified Medicines Directive. This directive covers prescription medicines sold in Germany, including most biologics.

Germany’s national verification system, securPharm, links to the EU hub and requires a unique identifier plus tamper-evident packaging on every pack.

Before you submit, your manufacturing site needs a current GMP certificate, either through EU mutual recognition or a direct EU GMP certificate. PEI and EMA inspectors will not accept outdated or non-EU-equivalent certification.

Biologics and Biosimilars Registration Process in Germany

Nine steps make up the Biologics Approval Process in Germany. The Biosimilars Approval Process in Germany follows the same route, since both run through the EU centralised procedure. Germany’s part of it doesn’t really start until EU approval is already in hand.

Step 1: Pre-Submission Preparation
Confirm that the product falls into a category eligible for EMA’s centralised procedure. Then request a CHMP pre-submission meeting if needed, and put together your full dossier in the required CTD format (the Common Technical Document, the standard structure regulators expect for a marketing authorisation dossier). This is also when you should confirm GMP inspection readiness at your manufacturing site.

Step 2: Dossier Submission to EMA
Submit your complete application, called the Marketing Authorisation Application (MAA), directly to EMA. Do not submit it to any German authority, since biologics fall under the mandatory centralised procedure

Step 3: Rapporteur and Co-Rapporteur Appointment
CHMP appoints a rapporteur and co-rapporteur (the two committee members who lead the scientific review) to lead the scientific review. PEI or BfArM assessors are often chosen for German-linked applications, giving Germany a direct voice in the review.

Step 4: Scientific Evaluation by CHMP
During the 210-day evaluation period, the rapporteur and co-rapporteur teams assess the quality, non-clinical and clinical data submitted in the application. At the same time, the Pharmacovigilance Risk Assessment Committee (PRAC) checks the Risk Management Plan.

Step 5: Clock-Stop Question Rounds
CHMP sends formal questions at Day 120 and again at Day 180. When this happens, the 210-day clock pauses until the applicant submits complete answers.

Applications are most likely to be delayed at this stage if the submitted data package is incomplete.The CHMP evaluation clock remains stopped until the applicant provides satisfactory responses to all outstanding questions.

Step 6: CHMP Opinion
By Day 210 (or Day 150 under accelerated assessment), CHMP gives its final opinion, for or against authorisation, based on the full review.

Step 7: European Commission Decision
The European Commission has 67 days from the CHMP opinion to issue the legally binding marketing authorisation. It applies across all EU countries, including Germany.

Step 8: National Implementation in Germany
Once approved, the product enters Germany’s national system. If it’s a vaccine, serum, allergen or blood/plasma product, PEI must release each batch under Section 32 AMG before it reaches the market. Most biosimilars skip this step. BfArM handles ongoing national tasks, like variations, for products under its remit.

Step 9: Local Regulatory Setup for Launch
A handful of things have to be locked in before the product reaches the German market. A Germany-based responsible person. Local pharmacovigilance contacts. Packaging that satisfies securPharm’s anti-counterfeiting rules. German-language labelling, finished and approved.

The marketing authorisation is EU-wide, so Germany doesn’t run a separate national approval track. But Steps 8 and 9 are where your German-specific readiness actually decides your launch date. And Step 8 only applies to certain product types.

Documents Required for Biologics and Biosimilars Registration

There are five modules that make up the dossier for Biological Medicinal Products Registration in Germany. All of these modules are built to the Common Technical Document format. The European Medicines Agency has adopted this structure from the ICH M4 guideline as the format for European Union applications.

Module 1 covers administrative information, including the application form, SmPC, labelling, and country-specific annexes. This module is region-specific, and the EU has its own version.

Module 2 covers the Quality Overall Summary, Nonclinical Overview and Clinical Overview, along with supporting tabulated summaries.

Module 3 covers quality documentation, including the manufacturing process and analytical methods. It is governed by ICH M4Q.

Module 4 covers nonclinical study reports, including pharmacology, pharmacokinetics and toxicology data. It is governed by ICH M4S.

Module 5 covers clinical study reports. It is governed by ICH M4E.

For biosimilars, your Module 2 and 3 quality data must show comparability to the reference product in much greater detail than a standard generic would need.

For Biologics there is more to the dossier than the information. It must also include a Risk Management Plan and a Pharmacovigilance System Master File describing how product safety will be monitored after approval. Detailed characterisation data is also necessary for Biologics. This data reflects the complexity of molecules.

Clinical Trial Requirements for Biologics and Biosimilars

Clinical trials for biologics and biosimilars in Germany must follow the Clinical Trial Regulation (EU) No. 536/2014. From 31 January 2023 all new clinical trial applications for Biologics and Biosimilars must be submitted through the Clinical Trials Information System (CTIS). EMA builds and maintains CTIS along with EU/EEA member states and the European Commission.

Every trial needs:

• Ethics Committee approval
• Full compliance with Good Clinical Practice (GCP) standards

For biosimilars, EMA’s biosimilar guideline (CHMP/437/04 Rev. 1) says the clinical focus is on comparability, not on proving efficacy from scratch. This usually means:

• PK/PD comparability studies against the reference product
• Immunogenicity testing, since biological molecules can trigger unwanted immune reactions that small-molecule generics don’t. EMA requires this to be tested using the same method and sampling schedule for both products.
• Full clinical efficacy trials, only when the analytical and PK/PD data still leave real doubt about biosimilarity

Labelling Requirements for Biologics and Biosimilars

Labelling for biologics and biosimilars in Germany must follow the EU QRD (Quality Review of Documents) templates. EMA confirms these are mandatory for all human medicines going through EU procedures.

They cover:

• Summary of Product Characteristics (SmPC)
• Package Leaflet
• Outer packaging text

German versions of all three are required for the German market, alongside the English master text used during the EU review.

The outer packaging must show:

• The invented name
• The active substance, including the biosimilar’s own trade name
• Batch number and expiry date
• Serialization elements required by the EU Falsified Medicines Directive, a unique identifier (Data Matrix Code) and an anti-tampering device, checked through securPharm before dispensing.

Start your German labelling translation well before Day 180. QRD review and German-language finalisation both need to happen in a tight window before the Commission decision.

Timeline for Biologics and Biosimilars Approval

The centralised procedure can take up to 210 days. That count doesn’t include clock stops, which are pauses in the timeline that happen whenever you need to provide more information to CHMP. Here are the key official milestones:

• Up to 210 days – standard CHMP evaluation
• Up to 150 days – accelerated assessment on request, for products of major public health interest
• 67 days – the European Commission’s decision period after a positive CHMP opinion

There is no official German timeline beyond this EU process for centrally authorised biologics. Where PEI batch release under Section 32 AMG applies (vaccines, sera, allergens, blood products), the testing schedule depends on PEI and isn’t published as a fixed legal timeframe.

If your product needs PEI batch release, build that time into your German launch plan separately from the EU approval timeline. For most biosimilars, this step doesn’t apply, so launch timing mostly depends on Steps 8-9 (local setup) instead.

Fees for Biologics and Biosimilars Registration

EMA publishes official fee schedules for the centralised procedure on its fees and charges pages.

These cover:

• Initial marketing authorisation fees
• Variation fees
• Annual fees

The amount you pay depends on a few factors:

• The legal basis of your application
• Whether the active substance is new or already known
• Whether you qualify for SME fee reductions

Fees are adjusted every year and they apply the same way across the whole EU, including for products sold in Germany. Germany does not have a separate national fee schedule for centrally authorised biologics. That’s because the authorisation itself comes from the EU, not from a German authority.

One exception is if PEI runs official batch testing under Section 32 AMG, that specific service has its own fee, set by PEI. Check current figures directly with PEI.

Post-Marketing Surveillance Requirements for Biologics and Biosimilars

Pharmacovigilance obligations begin the day the marketing authorisation takes effect, not after a grace period. The marketing authorisation holder must:

• Maintain a Pharmacovigilance System Master File (PSMF)
• Submit Periodic Safety Update Reports (PSURs) on the schedule set at authorisation
• Implement the agreed Risk Management Plan, including any post-authorisation safety studies
• Conduct continuous signal detection, reporting to EMA’s pharmacovigilance system
• Report adverse events occurring in Germany through the national system, which feeds into EudraVigilance
• Submit and gain approval for manufacturing variations before implementation
• Support ongoing GMP inspections, which continue throughout the product’s lifecycle
• Maintain batch traceability through securPharm serialization data and, where applicable, PEI batch release records

Conclusion

Biologics and Biosimilars Registration in Germany runs mainly through the EU centralised procedure, with PEI and BfArM handling specific national duties rather than a separate approval track. What actually determines your timeline is operational readiness, from GMP timing and Module 3 data to the right authority contact and pharmacovigilance systems ready before day one.

Whether you’re preparing your first submission or navigating a complex biosimilar comparability package, Artixio helps you navigate registration requirements, prepare documentation and plan your market entry strategy for Germany with guidance tailored to your product and project timeline. Reach out to us at info@artixio.com.

FAQs

Q1. Is a separate German marketing authorisation required for biologics already approved by EMA?
No. Once the European Commission grants a centralised marketing authorisation, it is valid in Germany automatically. Germany does not run a parallel national approval process for these products, though national tasks such as PEI batch release and local pharmacovigilance arrangements still apply.

Q2. What is the difference between PEI and BfArM for biologics regulation?
Under Section 77 of the AMG, PEI is Germany’s authority for vaccines, sera, allergens, blood and blood products, genetically engineered blood components and ATMPs. Official batch release testing under Section 32 AMG applies specifically to vaccines, sera and allergens. BfArM handles most other human medicinal products, including many biosimilars, and manages national procedural and pharmacovigilance coordination tasks.

Q3. How long does the biologics approval process take in Germany?
Since biologics go through the EU centralised procedure, the evaluation takes up to 210 days at EMA, followed by up to 67 days for the European Commission’s formal decision. Accelerated assessment can reduce EMA’s evaluation to 150 days for products of major public health interest. These are the only officially published timelines; there is no separate published German national timeline for centrally authorised biologics.

Q4. Do biosimilars need full clinical efficacy trials in Germany?
Usually not. Biosimilar approval relies primarily on analytical comparability, PK/PD comparability studies and immunogenicity data against the reference product. A full efficacy trial is only required when the analytical and PK/PD package leaves meaningful uncertainty about comparability.

Q5. Which language must labelling be in for the German market?
The SmPC, Package Leaflet and outer packaging must be provided in German, in addition to the English master text reviewed during the EU procedure, and must follow the official QRD templates.

Q6. Are biosimilars automatically interchangeable with the reference biologic in Germany?
No, not automatically. That decision sits with the Gemeinsamer Bundesausschuss (G-BA), the Joint Federal Committee, not with BfArM or PEI. The G-BA sets substitution and interchangeability rules for biosimilars at the pharmacy level, separately from the EU marketing authorisation itself. This is a distinct regulatory topic from registration and deserves its own dedicated article.