FAQ

ISO 19011 defines the term "audit" as a systematic, independent and documented process for obtaining objective evidence and evaluating it objectively.
For an audit conducted by the US health authority – the Food and Drug Administration (FDA) – checks are carried out on companies wanting to manufacture products relating to public health and sell them in the USA. This includes foodstuffs, pharmaceutical products, medical equipment and combination products, as well as cosmetics and tobacco products.
Depending on the audit, adherence to various standards, such as the ISO 9001 Quality Management Standard, will be checked as a benchmark in order to ensure fulfilment of the audit criteria on this basis.
rantronik is very happy to support you in preparing for the audit, during the audit and the in follow-up.
 

All interested parties have the opportunity to arrange auditing in their dealings in order to vet their commercial partners.
Health authorities such as the Food and Drug Administration (FDA) are responsible for approving and placing on the market goods that are within in their remit of responsibility. Goods can only be placed on the relevant market with the FDA's assent.
The FDA is responsible for the US market. It has the right to inspect and carry out checks on production facilities around the world where goods relating to public health are manufactured, in the case that these goods are to be exported to the USA. This inspection can either be conducted by the FDA itself, or by a local health authority.
 

There are various types of FDA audits:

Pre-approval audits: An audit is necessary in the first instance before a pharmaceutical product or a medical product is allowed to be placed on the market.

"For-cause" audits: These audits are inspections where there are grounds for suspicion. Possible reasons for this include, for example, complaints about the company, on the basis of which the audit is conducted. These generally unannounced audits by the authorities are used to check the grounds for suspicion promptly and are intended to minimise the risk to patients.

Routine audits: Most audits comprise routine checks, which are announced in advance to allow sufficient time for preparation.

If you are informed of an audit, you should prepare immediately and thoroughly for the inspection to be conducted by the authority. rantronik is happy to help you with the preparations and support you through the inspection process in order to ensure the audit runs as smoothly as possible.

The aim of an audit is to carry out checks on a company based on its business processes in the field of observation in order to determine whether the legal and regulatory requirements regarding GMP, DIN, EN and ISO standards are being observed. This includes standards for ensuring patient safety, as well as compliance with the legal regulations and specifications.
The company's methods, processes and systems and their efficient use are evaluated in an FDA audit using the Quality System Inspection Technique (QSIT).
To this end, the relevant processes are checked, employees are questioned and their activities are observed. Another important part of the audit is checking records in connection with the scope of the inspection. This includes, amongst other things, standards such as SOPs, evidence records such as proof of training, and calibration certificates.
 

Each audit differs depending on the audit criteria and interaction with the parties participating in the audit. For each company and each audit, there is therefore a unique configuration regarding the applicable requirements.
However, the following list of general information can, in principle, be used as a starting point for which records should be available at the beginning of the audit and which should be furnished at the request of the auditor:
 

• Overview of the company (history, locations, organigram, number of employees, products sold, etc.)
• Maps and flowcharts regarding the production location
• Structure in the USA (sales partners, wholesalers, etc.)
• Batch list of all products that have been placed on the market in the USA, including possible rejected batches
• SOP lists or extracts from Quality Management System (QMS), and key SOPs if applicable
• Lists of all deviations, OOS, complaints, change controls and AQRs affecting US products

A routine audit is usually announced several weeks in advance. All important documents should be made available for the inspection. At the beginning of an audit, the auditor explains the reason for the inspection before a walk-through of the production and laboratory facilities. Process documents, laboratory data, training records, and further documents undergo a review at the same time. At the end of the audit, the results of the inspection and shortcomings (observations), where applicable, are communicated and summarised in an audit report in the follow-up.
rantronik is happy to provide you with expert, reliable support throughout the entire audit process: From the planning and preparation stage, to the execution of the audit through to the necessary processing of the defined observations, where applicable.
 

If shortcomings (failings) are identified in an FDA audit, these will be documented on a form. This form has the FDA number 483, meaning that it is generally referred to as "a 483" in everyday usage. The company usually has 15 working days to respond to this form. If the failings are not rectified, the affected products are subject to a ban on production for the US market.
After the inspection, the auditor compiles an Establishment Inspection Report. The results are entered into the FACTS database after classification and are accessible to the public.
In the case of major failings, significant deviations from applicable standards, repeated violations or insufficient risk minimisation concerning the measures suggested by the company to rectify the failings, the FDA authority sends an official Warning Letter.
A Warning Letter has significant consequences. Generally, it indicates an import ban on the affected products on the US market. After a Warning Letter, a complete restructuring of the company is usually required. This leads to huge expenditure of time and resources.
In order to avoid this situation, effective preparation for an audit is imperative, for which rantronik is happy to offer you expert support.
 

The best, most reliable tip is always to act in accordance with applicable standards and practise consistent quality and risk management, even if there is no upcoming audit. During the audit, you should always consistently be honest, ask for clarification if anything is unclear, and argue rationally without trying to convince or deceive the inspector.
Reference should always be made to written documents and you should also log any documents copied by the auditor. It is imperative that the results discussed are taken seriously and failings are rectified in order to confirm to the auditor that the concerns raised are being taken seriously.
Training for inspections can hone awareness of the important aspects in advance, so that the chances of passing an audit without findings are significantly increased. rantronik is on hand to answer any questions regarding audits that your company may have.
 

rantronik supports companies throughout the entire inspection period, which comprises preparations for the inspection, the phase during the audit and any subsequent activities, which may include follow-up meetings, for example. Audit preparation tasks include, amongst others, the creation of storyboards, training catalogues and risk assessments for production equipment. Furthermore, staff training sessions and the establishment of testing plans and activities for ensuring data integrity are tasks that should already have been completed before the audit. During the audit, we will support your company and ensure the process runs as smoothly as possible between you and the auditor, with the aim of achieving zero findings. rantronik is also happy to continue advising you after the audit in order to ensure process compliance with the regulations and thereby guarantee high product quality in the long term.
 

After the transitional periods have come to an end, the labelling of all medical products must be fully changed over; if this is not yet complete, distribution of these products in the EU will no longer be permitted.

rantronik would be happy to share its expertise based on its vast experience, and offers you comprehensive support for implementing the new MDR.

The MDR is due to come into effect from May 2020.

There are, however, separate regulations governing the different product classes subject to the MDR.

If you require more detailed information, feel free to contact rantronik.

Please refer to the link below for an overview of the most significant changes resulting from the changeover to the MDR:

https://www.tuev-sued.de/produktpruefung/branchen/medizinprodukte/marktzulassung-und-zertifizierung/eu-marktzugang/mdr-eu-medizinprodukteverordnung

Several factors have to be taken into account here:

The test standard to be applied and the code size influence which printing system is chosen. This, in turn, has to be adapted to the printing surface.

rantronik is happy to assist you whatever your needs, and works together with you to develop the perfect integrated solution

Thanks to our experience gained through various collaborative projects in the UDI sector, we are also able to provide targeted support for your company in implementing the necessary UDI measures. The focus here is not only on meeting the legal deadlines but also on continuously adapting the whole process. We firstly create a tailored project plan including all the necessary steps. On request, rantronik can advise you in adapting existing plant and labelling systems, changing over software and hardware, system integration, data management and logistics.

Various printing systems, such as laser marking, thermal transfer or inkjet printing, are used for UDI printing.

An analysis with various print tests is necessary for choosing the correct printing system.

An analysis performed by rantronik is used to determine whether the technical performance of the existing system is suitable for conversion to UDI while complying with the applicable CE provisions and the currently applicable Machinery Directive. This analysis does of course also incorporate the economic assessment of the investment in the system requiring conversion. The detailed analysis report then goes on to form the basis for deciding whether to convert the existing system or purchase a new one.

In this case, changing the material of the printing surface (substrate) in question, attaching certain special labels or changing the printing technology makes it possible to fulfil UDI requirements.

When choosing a test standard, the decisive factor is whether the 2D matrix code is printed on the product itself or whether it is applied to secondary packaging, e.g. by means of a label.

The following test standards are usually applied:
ISO/IEC TR 29158:2011 DPM (Direct Part Mark)
ISO/IEC 15415:2011

When the product is delivered, each 2D matrix code must have a certain grading that can be verified with specialist test devices that comply with the relevant standards.

rantronik boasts extensive expertise and can assist in verification processes with its own test devices.

Some providers offer test devices that comply with the relevant standards for in-line and offline checks; however, when making your selection, you should note the scope of testing required for the product in question (frequency of testing and type of testing specified by test standard).

To ensure a stable labelling process, it is essential to perform both regular and random tests (IPCs).

rantronik defines the required test processes and workflows together with you, draws up all the necessary documentation and assists in the training of staff.

The requirements of the FDA mean that each individual product has to be labelled on delivery in line with the required UDI quality.

The extent of the quality checks should be determined on the basis of risk and is governed by the universally applicable standards as well as the specific circumstances of the labelling process in question.

Serialisation refers to the clear assignment of a unique identification number to all packaging. This identifier is printed in a machine-readable format. With Directive 2011/62/EU, the EU has published a catalogue of measures which obligates pharmaceutical producers to affix specific labelling to packaging to safeguard medicines against tampering and falsification. The 2D barcode that is mainly used in accordance with the GS1 standard contains certain details such as the product identifier or the expiry data. When combined with data storage in national and European database systems, this code enables safety checks to be carried out at all stages of the supply chain.

Since 9th February 2019, prescription medicines have required a unique serial number in order to be distributed in the EU.

Serialisation is primarily intended to safeguard the safety of patients and staff in the healthcare sector by protecting against falsified medicines. In addition, countless business processes in production, logistics and accounting are presented in a simpler and more transparent way.

To comply with the requirements from EU Directive 2011/62/EU, a variety of process changes and investment measures are needed. For each single sales unit, a unique serial number has to be obtained, the code affixed and the information uploaded to the relevant databases. This can result in changes to systems including control systems, the packaging material, printing or laser technology, staff, IT architecture, quality management and other areas.

As is the case with every project, the first step is project planning, including defining the individuals responsible for the project and the objectives of the project. Codes and approvals should then be obtained from the relevant authorities. In most cases, investment then has to be made in software, hardware and systems including control systems, and production and packaging technology has to be adapted. The implementation of an IT system for continuous data management should not be overlooked at this point. Lastly, changes to the packaging with regard to the print and protection against tampering have to be made and staff have to be trained in the amended procedures.

rantronik is your expert partner when it comes to questions relating to serialisation and provides advice on issues such as how to obtain codes and approvals and exchange with the relevant authorities, approval of the print layout or the procedure for reports and assessments.
We collaborate with you to take stock of your existing resources and plan the necessary adaptations in production and IT. We would also be happy to help you with any questions you might have relating to preparing and managing the relevant data and uploading it to the EU Hub.

Both the unique serial number and the product code, batch designation, national reimbursement or identification number and the expiry date must be represented by the code in machine-readable and human-readable form.

Various direct labelling systems such as inkjet printers, laser markers or preprinted adhesive labels are possible depending on the characteristics of the packaging material, the contrast between the print and the surface of the packaging, the production speed and the wear resistance of the coding. rantronik would be happy to advise you on the ideal solution for your serialisation project.

First of all, the technical performance of the existing system is analysed. Necessary changes, conversions or adaptations are listed, taking account of the impact on EU regulations and the specifications from the Machinery Directives.
This makes it possible to demonstrate a comparison of the costs of the required measures in the existing system compared to investment in a new system. This is then used as the basis for specific decision-making in your company.

The directive does not expressly prescribe a specific test standard, meaning that the test standard options from GS1 using PPN, gluing of folding boxes, void seals and tamper evident labels should suffice. The codes used have one- or two-dimensional code structures (1D/2D codes) or the frequently used Data Matrix ECC200 code.

The print quality must achieve a grading of at least 1.5 as per the ISO/IEC 15415:2011 standard, which equates to grading C.

To ensure that the requisite quality of the print is kept consistently high, regular random checks (IPCs) are necessary. rantronik can help you to define the required test processes and workflows, compile documentation, train your staff or find the appropriate standard-compliant test equipment for inline and offline checks. rantronik has its own code reading and verification equipment.

The EU Falsified Medicines Directive stipulates that every single product or every single item of packaging has to be checked. This refers to a full check.