An Essential Guide to the Graduated Plan Officer (Der Stufenplanbeauftragte)

Introduction

According to §63a of the German Medicinal Products Act (AMG), a pharmaceutical entrepreneur who places finished medicinal products on the market that are medicinal products within the meaning of §2 section 1 or section 2 no. 1 AMG must appoint a qualified person resident in a member state of the European Union with the necessary expertise and reliability to carry out their activities (Graduated Plan Representative). In addition to marketing authorization holders (MAH), this also applies to co-distributors and users of standard marketing authorizations, as they are also pharmaceutical entrepreneurs pursuant to §4 section 18 AMG and place medicinal products on the market under their name.

A pharmaceutical company that only has central marketing authorizations does not need a graduated plan officer. In this case, the EU QPPV is sufficient, which assumes the tasks of the graduated plan officer to the extent of the obligations under Art. 23 of Regulation (EC) No. 726/2004 and article 104 of Directive 2001/83/EC.

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For the other obligations of a GPO, some of which go beyond the tasks of the EU QPPV the pharmaceutical company must ensure that a person is appointed to assume these duties. Such duties are the systematic recording and analysis of complaints and reporting of recalls.

If the EU QPPV does not speak German, this supporting person should assist the EU QPPV linguistically or through language mediation.

Even if this supporting person is not a graduated plan officer him/herself, he/she will be tasked with performing the duties of the graduated plan officer.

Local Registration of the GPO

In accordance with § 63a AMG, a graduated plan officer (equivalent to the EU QPPV) for national marketing authorizations and marketing authorizations from decentralized procedure (DCP) or the mutual recognition procedure (MRP) must be registered with the competent authority ("Landesbehörde"- federal state authority) and the competent higher federal authority ("Bundesinstitut für Arzneimittel und Medizinprodukte - BfArM" and/or the “Paul-Ehrlich-Institut - PEI”, if applicable) for the scope of the AMG.

The Paul-Ehrlich-Institut (PEI), Federal Institute for Vaccines and Biomedicines, is responsible for the following medicinal products (§ 77 AMG):

• Sera
• Vaccines
• Blood preparations
• Tissues and tissue preparations
• Allergens
• Advanced therapy medicinal products (gene therapy medicinal products, somatic cell therapy medicinal products and bioengineered tissue products)
• Xenogeneic medicinal products
• Genetically engineered blood components

The Federal Institute for Drugs and Medical Devices (BfArM) is responsible for all other medicinal products intended for human use.

If the pharmaceutical company/MAH has its location in Germany, the corresponding state authority must also be informed about the registration of the GPO. In case the pharmaceutical company/MAH is located in another EU-country, the registration of the GPO is only done at the BfArM or PEI.

The registration of the graduated plan officer in accordance with § 63a section 3 AMG takes place via the PharmNet.Bund portal "Registration of the graduated plan officer".

The PharmNet Bund Reporting Portal is used to report graduated plan officers, deputies, change notifications of persons or contact details, as well as to deregister the named persons and implement the requirements of the Online Access Act (OZG). All information on the graduated plan officer or the person responsible for performing the duties of the graduated plan officer within the context of the AMWHV also applies to deputies.

The German Legislation

The local legislation is based on the German Medicinal Products Act (Arzneimittelgesetz, AMG) - §63a Graduated Plan Officer and the Ordinance on the Manufacture of Medicinal Products and Active Substances (Arzneimittel- und Wirkstoffherstellungsverordnung, AMWHV) - §19 Complaints and Recalls 

German Medicinal Products Act (Arzneimittelgesetz, AMG) - §63a Graduated Plan Officer - English content translation 

1. Anyone who, in his/her capacity as a Pharmaceutical Entrepreneur, places finished medicinal products on the market, must appoint a qualified person who is resident in a Member State of the European Union, who has the required expert knowledge and the reliability necessary for exercising his/her function (graduated plan officer) to set up and manage a pharmacovigilance system and to collect and evaluate notifications on medicinal product risks that have become known and co-ordinate the necessary measures. Sentence 1 does not apply to persons who do not require a manufacturing authorization according to § 13 section 2 number 1, 2, 5 or section 2b.  
   The Graduated Plan Officer is responsible for meeting the obligations to notify insofar as they concern medicinal product risks. He/she must also ensure that additional information for the evaluation of the risk-benefit profile of a medicinal product, including his/her own evaluations, are sent immediately and in full, if requested by the competent higher federal authority. The details are stipulated by the Ordinance on the Manufacture of Medicinal Products and Active Substances (Arzneimittel- und Wirkstoffherstellungsverordnung). Persons other than those specified in sentence 1 are not authorized to perform the duties of the Graduated Plan Officer. 
2. The Graduated Plan Officer may also be a qualified person according to §14 or a person responsible according to § 20c at the same time. 
3. The Pharmaceutical Entrepreneur must notify the competent authority and the competent higher federal authority about the identity of the Graduated Plan Officer and must make notification of any change beforehand. In the case of an unforeseen change in the person of the Graduated Plan Officer, notification is to be made immediately. 

Ordinance on the Manufacture of Medicinal Products and Active Substances (Arzneimittel- und Wirkstoffherstellungsverordnung, AMWHV) - §19 Complaints and Recalls - English content translation 

1. The Graduated Plan Officer is responsible for collecting all known notifications of drug risks by means of a written or electronic procedure and of systematically recording all complaints. Immediate review of the reports shall be promptly made and assessed as to whether a drug risk exists, the severity of the risk, and the measures to be taken. The necessary measures are to be coordinated and made known to the Qualified Person (QP) according to § 14 of the German Drug Law, so that the necessary measures can be taken, if necessary, in particular if the problem could be a quality problem. The effectiveness of the procedures shall be reviewed regularly. 
2. The Graduated Plan Officer shall inform the competent authority immediately of any deficiency which could lead to a recall or an unusual restriction on the distribution and shall also indicate to which countries the medicinal product has been shipped or has been exported.  
   In addition, the authority must also be informed immediately of any suspicion of falsification of medicinal products or active substances; in the case of medicinal products for human use, the holder of the authorization shall also be informed. 
3. The Graduated Plan Officer must fulfill the reporting obligations under the Medicines Act insofar as they relate to drug risks. The reporting obligations pursuant to Section 14 of the GCP Ordinance in the version applicable on the day before its expiry pursuant to Article 13 Paragraph 4 of the Fourth Law Amending Pharmaceutical Law and Other Regulations of December 20, 2016 (Federal Law Gazette I p. 3048) remain unaffected. 
4. Paragraph 1 applies accordingly to investigational medicinal products. The Graduated Plan Officer is responsible for ensuring that, in collaboration with the Sponsor, complaints are systematically recorded and reviewed and that effective systematic precautions are taken so that further use of the investigational medicinal products can be prevented, if necessary. Any defect that could lead to a recall or an unusual restriction on sales must be documented and investigated and the responsible authority must be informed immediately and also communicated to which testing centers within or outside the scope of the Medicines Act the investigational product was delivered. If the investigational medicinal product is an approved medicinal product, the Graduated Plan Officer, in collaboration with the Sponsor, must inform the Marketing Authorization Holder of any defect that may be associated with the approved medicinal product. 
5. The Graduated Plan Officer must keep records of the content of the reports, the type of review and the findings gained, the result of the assessment, the coordinated measures, and the notifications. 
6. The Graduated Plan Officer should be independent of the sales or distribution units and can only be represented by people who have the expertise in accordance with Section 63a paragraph 1 sentence 1 of the Medicines Act and must be in the area of application of the Medicines Act or in another reside and operate in a member state of the European Union. 
7. If a Pharmaceutical Entrepreneur places products on the market other than those mentioned in Section 63a Paragraph 1 Sentence 1 of the Medicines Act, he must appoint an appropriate person to carry out the tasks of the Graduated Plan Officer. The person appointed accordingly is responsible for compliance with the obligations under paragraphs 1 to 5. 
8. The Pharmaceutical Entrepreneur must ensure that all reports received in the company about drug risks and complaints as well as information for the assessment of the benefit-risk ratio of a drug are immediately communicated to the Graduated Plan Officer or the person appointed accordingly in accordance with paragraph 7 sentence 1 become. 
9. Paragraphs 1 to 3 and 5 to 8 apply accordingly to auxiliary preparations within the meaning of Article 2 paragraph 2 numbers 8 and 10 of Regulation (EU) No. 536/2014. 

Understanding the Local Requirements

Here are some common questions about the local requirements for GPO.

At what point in time is an GPO required

After marketing authorization approval, before launch the marketing authorization holder has to ensure that local literature search is performed. However, the Graduated Plan Officer is only required once product launch starts.

Specific for centrally authorized products the EU QPPV can serve as the GPO for certain tasks and no GPO needs to be appointed.

Is the GPO required to reside in Germany?

No, this is not necessary. The Graduated Plan Officer shall reside and operate in a Member State of the European Union.

Does the GPO need to speak fluent German?

There are no language requirements in the AMG. However, since communication with the authorities is predominantly in German, the Graduated Plan Officer, unless she/he speaks German her-/himself, shall have access 24 hours a day to a suitably qualified person.

What education shall the GPO have?

The Graduated Plan Officer must be sufficiently knowledgeable; a specific proof of knowledge is not (or no longer) required. The person must have sufficient professional qualifications to ensure compliance with the relevant regulations, in particular the company pharmacovigilance system.

This qualification can be acquired through professional training and practical experience. The professional qualification is assessed on a case-by-case basis and should be based on the product portfolio of the pharmaceutical company and the assessment of the possible drug risks associated with it (§ 19 Para. 1 AMWHV). Further details on this must be agreed with the competent state authorities.

Does the GPO need to be available 24/7?

Yes, the Graduated Plan Officer must be available 24/7 for the Competent Authorities.

Is a Deputy GPO required?

No, it is not required as per legislation. However, for business contingency purposes it is recommended to have a deputy GPO available.

Regarding the notification of the deputy GPO to the BfArM, there is no legal obligation. The AMG requires the notification of the GPO, but not explicitly that of the deputy. Nevertheless, it is desirable for smooth communication between the authority and the pharmaceutical entrepreneur to also contact the deputy GPO officer directly, if necessary. Therefore, it would save time and effort if the contact details of the deputy are also known.

Key Takeaways About the GPO

The GPO is like the QPPV, the key person to implement and maintain local, German PV processes and systems and to oversee the benefit risk profile of your products. Their tasks and responsibilities on national level are comparable to those of the QPPV on global level, including the systematic recording of complaints as well as informing the competent local authority of any defect that could lead to a recall or unusual restriction of distribution.

The GPO is therefore not only relevant for the PV system but also an important key role in the quality system and the interaction with the Competent Authorities. The complexity of the role and the very specific local registration process may be a difficult burden to Marketing authorization holders.

If you need GPO support, ProPharma has a well-established QPPV Office team which includes colleagues qualified for the QPPV role, as well as colleagues who are qualified to support you as a GPO. Please reach out to ProPharma for any support and contact the team at ProPharma today.

Sources

• Medicinal Products Act
• Verordnung über das Inverkehrbringen von Arzneimitteln ohne Genehmigung oder ohne Zulassung in Härtefällen/Ordinance on the marketing of medicinal products without authorization or without authorization in hardship cases (Only available in German)
• Stufenplanbeauftragter/Pharmacovigilance Officer
• Notification of the graduated plan officer